EA016912B1 - Aryloazol-2-ylcyanoethylamino compounds, method of making and method of using same - Google Patents

Abstract

The present invention relates to novel aryloazol-2-ylcyanoethylamino derivatives of formula (I), wherein R, R, R, R, R, P, Q, V, W, X, Y, Z and a are as defined in the description, compositions thereof, processes for their preparation and their uses as pesticides.

Description

The control of parasites, in particular endoparasites that infect animal parasites, by means of active substances containing a cyanoethylamino group, is described in many patents or patent applications, for example 1p1egiaboya1 Pa1ei1 PuBnciopk No. AO 2004/024704 (US Pat. , AO 2005/121075 and AO 2006/043654, as well as in EP 953565 (US patent 6239077) and EP 1445251.

However, none of the previous publications have written that the compound of formula (I) is active as pesticides, especially for controlling endoparasitic parasitic insects inside or on animals and ectoparasitic parasitic insects on animals.

SUMMARY OF THE INVENTION

The present invention relates to a cyanoethylamino derivative of the formula (I) aryloazol-2-ylk derivative new

where P is C-Κι or Ν;

O represents CK ₂ or Ν;

V represents CK ₈ or Ν;

A represents CK ₉ or Ν;

X represents CK _{! 0} or Ν;

Υ represents C-K11 or Ν;

K ₁ , K ₂ K ₈ , K ₉ , K ₁₀ and Kp, both together and independently from each other, represent hydrogen, amino, amido, cyano, nitro, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, phenoxy, alkoxyalkoxy, cycloalkyloxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulphinyl, halogenoalkylsulphinyl, alkylsulphonyl, alkylamino, di (alkyl) amino, alkylcarbonylamino, alkylaminoalkoxy, dialkylaminoalkoxy, alkylaminoalkyl, dialkylaminoalkyl, aminoalkyl, formyl, HO ₂ St. al yl-O ₂ C-, a substituted or unsubstituted aryl or a substituted or unsubstituted phenoxy, whereby each substituent may independently be selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio , alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl;

K3, K4 and K5, each independently of one another, are hydrogen, halogen, alkyl, hydroxyalkyl, alkylthioalkyl, haloalkyl, alkyloxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkylsulfonyloxyalkyl, unsubstituted or substituted cycloalkyl, in which the substituents can be and are independently selected from the group consisting of halogen and alkyl, unsubstituted or substituted phenyl, whereby each of the substituents can be independent of each other and be selected from the group consisting of cyano, nit ro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, or

K4 and K5 together with the carbon atom to which they are attached form a cycloalkyl ring;

K6 represents hydrogen, alkyl, alkoxyalkyl, alkylcarbonyl, alkylthiocarbonyl or unsubstituted or substituted benzyl, as a result of which the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, di (alkyl) amino;

K7 represents hydrogen, alkyl, alkoxyalkyl, alkylcarbonyl, alkylthiocarbonyl or unsubstituted or substituted phenyl, in which the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, alkyl, halogenated, phenyl, phenoxy, alkylthio , haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcar

- 1 016912 bonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, di (alkyl) amino; unsubstituted or substituted hetaryl, in which each of the substituents may be independent of one another and selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, di (alkyl) amino; or unsubstituted or substituted naphthyl or quinolyl, in which each of the substituents may be independent of one another and selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, di (alkyl) amino;

ζ is an ordinary bond, C (O), C (8) or 8 (O) _P ;

a represents 1, 2 or 3;

p represents 0, 1 or 2.

The aim of the present invention is the provision of new compounds, which are pesticides, from the family of aryloazol-2-ylcyanoethylamine, as well as methods for their preparation.

The second objective of the present invention is the provision of pesticide compositions and methods for producing pesticides based on aryloazol-2-ylcyanoethylamine, which is a pesticide, for controlling agricultural pests that are well tolerated by warm-blooded species, fish and plants, including especially for controlling endo- and ectoparasites that infect parasites of mammals, fish and birds.

Another objective of the present invention is the provision of compounds with high activity and increased safety for the user and the environment, which is achieved by optimizing chemical, physical and biological properties, such as solubility, melting point, stability, electronic and spatial parameters, etc.

To achieve the objectives of the present invention, unless otherwise specified in the specification, the following terms are defined as follows.

1. Alkyl refers to both linear and branched carbon chains; references to individual alkyl groups refer to a linear chain (e.g., butyl = n-butyl). In one embodiment, the alkyl contains 1-20 carbon atoms, in another embodiment, the number of carbon atoms in the alkyl is 1-8, and in another embodiment, the number of carbon atoms in the alkyl is 1-4. Other ranges of the number of carbon atoms are also considered depending on the location of the alkyl substituent in the molecule.

2. Alkenyl refers to both linear and branched carbon chains that have at least one carbon-carbon double bond. In one embodiment, the implementation of alkenyl, it contains 1-3 double bonds, in another embodiment, the number of double bonds in alkenyl is equal to one. In one embodiment, the number of carbon atoms in alkenyl is 2-20, in another embodiment, the number of carbon atoms in alkenyl is 2-8, and in another embodiment, the number of carbon atoms in alkenyl is 2-4. Other ranges of the number of carbon-carbon double bonds are also considered depending on the location of the akenyl substituent in the molecule.

3. Alkynyl refers to both linear and branched carbon chains that have at least one carbon-carbon triple bond. In one embodiment, the implementation of alkynyl, it contains 1-3 double bonds; in another embodiment, the number of double bonds in alkynyl is one. In one embodiment, the number of carbon atoms in alkynyl is 2-20, in another embodiment, the number of carbon atoms in alkynyl is 2-8, and in another embodiment, the number of carbon atoms in alkenyl is 2-4. Other ranges of the number of carbon-carbon triple bonds the number of carbon atoms is also considered depending on the location of the acinyl substituent in the molecule.

4. Aryl refers to a C ₆ -C _{1 0} aromatic ring structure. In one embodiment, the implementation of the aryl residue is phenyl, naphthyl, tetrahydronaphthyl, phenylcyclopropyl and indanyl; in another embodiment, the aryl residue is phenyl. Aryl refers to aryl substituted at two adjacent positions.

5. Alkoxy refers to —O-alkyl in which the alkyl is as defined in claim 1.

6. Alkanoyl refers to formyl (-C (= O) H) and -C (= O) alkyl, where the alkyl is as defined in claim 1.

7. Alkanoyloxy refers to —O — C (═O) alkyl, wherein alkanoyl is as defined in claim 6.

8. Alkanoylamino refers to —NH ₂ —C (= O) alknl, where alkanoyl is defined in claim 6 and the amino (XH ₂ ) residue can be substituted with alkyl as defined in claim 1.

9. Aminocarbonyl refers to —CH ₂ —C (═O), where the amino (XH ₂ ) moiety may be substituted with alkyl as defined in claim 1.

- 2 016912

10. Alkoxycarbonyl refers to —C (═O) —O-alkyl, wherein alkoxy is as defined in claim 5.

11. Alkenoyl refers to —C (= O) alkenyl, where alkenyl is as defined in claim 2.

12. Alkynoyl refers to -C (= O) alkynyl, where the alkynyl is as defined in claim 3.

13. Aroyl refers to -C (= O) aryl, where aryl is as defined above.

14. A cycle as a prefix (for example, cycloalkyl, cycloalkenyl, cycloalkynyl) refers to saturated or unsaturated cyclic ring structures containing from three to eight carbon atoms in the cycle, the boundaries of which tend to be separated and different from the definition of aryl given above. In one embodiment, the cyclo sizes are in the range of 4-7 carbon atoms; in another embodiment, cyclo sizes are in the range of 3-4. Other ranges of carbon atom numbers are also considered depending on the location of the cyclic residue in the molecule.

15. Halogen means fluorine, chlorine, bromine and iodine atoms. The designation halogen (for example, as demonstrated in the term haloalkyl) refers to all degrees of substitution from single substitution to perhalogen substitution (for example, as demonstrated for methyl as chloromethyl (-CH ₂ C1), dichloromethyl (-CHC1 ₂ ), trichloromethyl (-CC1 ₃ )).

16. Heterocycle, heterocyclic or heterocyclo belong to fully saturated or unsaturated cyclic groups, including aromatic (eg, hetaryl), for example, 4-7 membered monocyclic, 7-11 membered bicyclic or 10-15 membered tricyclic ring systems that contain at least one heteroatom in at least one cycle containing carbon atoms. Each cycle of a heterocyclic group containing a heteroatom may contain 1, 2, 3 or 4 heteroatoms selected from nitrogen atoms, oxygen atoms and / or sulfur atoms, in which nitrogen and sulfur heteroatoms may optionally be oxidized and nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be attached to any of the heteroatoms or to the carbon atom of the ring of the cyclic system.

Typical monocyclic heterocyclic groups include pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, thiadiazolidiazolidiazolidiazolidinyl , piperazinyl, 2-oxo-piperazinyl, 2-oxo-piperidinyl, 2-oxo-pyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thi morpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl, triazinyl and the like. n.

Typical bicyclic heterocyclic groups include indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, e.g. , furo [2,3c] pyridinyl, furo [3,2-b] pyridinyl or furo [2,3-b] pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (e.g. 3,4-dihydro-4-oxoquinazolinyl), tetrahydroquinolinyl and t .P.

Typical tricyclic heterocyclic groups include carbazolyl, benzidolyl, phenanthroinyl, acridinyl, phenanthridinyl, xanthenyl, etc.

Unless otherwise indicated or obvious from the context, the active agent or active ingredient or therapeutic agent, as used in this specification, refers to the aryloazol-2-ylcyanoethylamine derivative of the present invention.

Compounds of the present invention are intended to include racemic mixtures, single stereoisomers and tautomeric forms of the compound. Another aspect of the present invention is a salt form of a compound of the present invention.

Another aspect of the present invention is a solid form of a compound of the present invention, which consists of crystalline forms selected from the group consisting of single crystals, nanocrystals, co-crystals, molecular complexes, hydrates, hypohydrates, solvates, desolvates, clathrates and inclusion complexes and non-crystalline forms selected from the group consisting of non-crystalline glass and non-crystalline amorphous forms.

In addition, it is indicated that the present invention does not intend to cover within the scope of the invention any previously disclosed product, a method for producing this product that meets the written description and the requirements for the description of the claimed invention I8PTO (35 I. 8. the first paragraph) or EPO (paragraph 83 of the EPC), so that the applicant (s) retains the right and thus announces the rejection of any previously described product, the method of obtaining this product and the method of application of this product.

It is indicated that in this disclosure and especially in the claims and / or paragraphs, such terms as contains, contains, contains and the like may have the meaning ascribed to them in Patent Law I8; for example, they can mean includes, included

- 3 016912 or including and the like; and that terms such as consisting primarily of and consist primarily of have the meaning ascribed to them by Patent Law I8, for example they include elements that are implicitly listed, but exclude elements represented by the prior art or those that affect the main or new features of the present invention.

These and other embodiments are disclosed or become apparent and encompassed by the following detailed description.

The implementation of the invention

A first aspect of the invention provides novel aryloazol-2-ylcyanoethylamine derivatives of formula (I)

where P is C-Κι or Ν;

O represents CK ₂ or Ν;

V represents CK ₈ or Ν; represents CK ₉ or Ν; X represents C-Kyu or Ν;

Υ represents C-Kc or Ν;

Κι, K ₂ K ₈ , K ₉ , Kyu and Its, each independently of one another, are hydrogen, amino, amido, cyano, nitro, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, phenoxy, alkoxyalkoxy, cycloalkyloxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulphinyl, halogenoalkylsulphinyl, alkylsulphonyl, alkylamino, di (alkyl) amino, alkylcarbonylamino, alkylaminoalkoxy, dialkylaminoalkoxy, alkylaminoalkyl, dialkylaminoalkyl, aminoalkyl, formyl, HO ₂ C-, alkyl -O ₂ C-, n unsubstituted or substituted aryl or unsubstituted or substituted phenoxy, as a result of which the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl;

K ₃ , K ₄ and K ₅ , each independently of one another, are hydrogen, halogen, alkyl, hydroxyalkyl, alkylthioalkyl, haloalkyl, alkyloxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkylsulfonyloxyalkyl, unsubstituted or substituted cycloalkyl, in which the substituents may be independent each other and be selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl, halogenated ynyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, di (alkyl) amino; or

K4 and K5 together with the carbon atom to which they are attached form a cycloalkyl ring;

K ₆ represents hydrogen, alkyl, alkoxyalkyl, alkylcarbonyl, alkylthiocarbonyl or unsubstituted or substituted benzyl, in which the substituents may be independent from each other and be selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, di (alkyl) amino;

K ₇ represents hydrogen, alkyl, alkoxyalkyl, alkylcarbonyl, alkylthiocarbonyl or unsubstituted or substituted phenyl, in which the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, alkyl, halogenated, phenyl, phenoxy, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, di (alkyl) amino; unsubstituted or substituted hetaryl, in which the substituents can be independently selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfonyl, alkylsulfonyl haloalkylsulfonyl, alkylamino, di (alkyl) amino; or unsubstituted or substituted naphthyl or quinolyl, in which the substituents may be independent of one another and selected from the group consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonylalkyl, haloalkyl , haloalkylsulfinyl, alkylsulfonyl, alkylamino, di (alkyl) amino;

ζ is an ordinary bond, C (O), C (8) or 8 (O) _P ;

a is 1, 2 or 3;

p represents 0, 1 or 2.

In one embodiment of the first aspect of the invention, new manufacturing facilities are provided.

- 4 016912 aryloazol-2-ylcyanoethylamine of the formula (I), where

P represents SI ₁ or Ν;

O represents CI ₂ or Ν;

V represents SI ₈ or Ν;

V represents CK ₉ or Ν;

X represents SI ₁₀ or Ν;

Υ represents SI ₁₁ or Ν;

Κι, And ₂ Κ _10, and Itz, each independently of one another, are hydrogen, amino, amido, cyano, nitro, halogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₇ cycloalkyl, hydroxy-C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ alkoxy, phenoxy, C | -C6-alkoxy-C | -C6-alkoxy, C3-C7-cycloalkyloxy, halogen-C | -C6-alkoxy, C | -C6 -alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkylsulfinyl, halogen-C ₁ -C ₆ -alkylsulfinyl, C ₁ -C ₆ -alkylsulfonyl, C | -C6-alkylamino, di (C | -C6-alkyl) amino, C | -C6 -alkylcarbonylamino, C | -C6-alkylaminoalkoxy, di-C | -C6-alkylaminoalkoxy, C | -C6-alkylaminoalkyl, di-C | -C6-alkylaminoalkyl, amino-C | -C6 -alkyl, formyl, HO ₂ C-, C ₁ - C ₆ -alkyl-O ₂ C-, unsubstituted or substituted aryl or unsubstituted or substituted phenoxy, as a result of which each of the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, C | -C6 -alkyl, halogen-C | -C6 -alkyl, C | -C6 -alkylthio, halogen-C | -C6 -alkylthio, arylthio, C | -C6-alkoxy, halogen-C | -C6-alkoxy, C | -C6-alkylcarbonyl , halogen-C | -C6 -alkylcarbonyl, C | -C6 -alkylsulfinyl, alogi-C | -S6-alkylsulfinyl, C | -S6-alkylsulfonyl, halo-C | -S6-alkylsulfonyl;

Β ₃ , And ₄ and And ₅ , each independently from each other, are hydrogen, halogen, C ₁ -C ₆ -alkyl, hydroxy-C | -C6-alkyl, C | -C6-alkylthio-C | -C6- alkyl, halogen-C | -C6 -alkyl, C | -C6-alkyloxy-C | -C6-alkyl, C | -C6-alkylsulfinyl-C | -C6-alkyl, C | -C6-alkylsulfonyl-C | -C6 -alkyl, C | -C6-alkylsulfonyloxy-C | C6 -alkyl, unsubstituted or substituted by C3-C7-cycloalkyl, in which the substituents can be independent from each other and be selected from the group consisting of halogen and C _| -C ₆ -alkyl, unsubstituted or substituted phenyl, as a result of which each of the substituents can be independent of each other and be selected from the group consisting of cyano, nitro, halogen, C _| -C ₆ -alkyl, halogen-C _| C6-alkyl, C | -C6 -alkylthio, halogen-C | -C6 -alkylthio, arylthio, C | -C6-alkoxy, halogen-C | -C6-alkoxy, C | C6-alkylcarbonyl, halogen-C | -C6 -alkylcarbonyl, C | -C6 alkylsulfinyl, halogen-C | -C6 alkylsulfinyl, C | -C6-alkylsulfonyl, halogen-C | -C6-alkylsulfonyl, C | -C6-alkylamino, di (C | -C6alkyl) amino; or

And ₄ and together with the carbon atom to which they are attached form a cycloalkyl ring;

And ₆ is hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ C6 alkylthiocarbonyl or unsubstituted or substituted benzyl, in as a result, each of the substituents can be independent of each other and be selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylthio , halogen-C ₁ -C ₆ alkylthio, arylthio, C ₁ -C ₆ alkoxy, halogen-C ₁ -C ₆ alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C _{1 C6-alkylsulfinyl,} halo-C1-C6-alkylsulfinyl, C1-C6 alkilsul Onila, halo-C1-S6alkilsulfonila, C1-C6-alkylamino, di (C1 -C6 alkyl) amino;

And ₇ is hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ C6 alkylthiocarbonyl or unsubstituted or substituted phenyl, in as a result, the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, C1-C6 alkyl, halogen-C1-C6-alkyl, phenyl, phenoxy, C1-C6-alkylthio, halogen-C1 -C6-alkylthio, arylthio, C1-C6-alkoxy, halogen-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1 -alkylsulfonyl, halogen en-C1-C6 alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino; unsubstituted or substituted hetaryl, in which each of the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, C1-C6 alkyl, halogen-C1-C6-alkyl, C1-C6-alkylthio, halogen C1-C6-alkylthio, arylthio, C1-C6-alkoxy, halogen-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfonyl C6-alkylsulfonyl, halogen-C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino; or a substituted or unsubstituted naphthyl or quinolyl, wherein each of the substituents may be independent of one another and be selected from the group consisting of cyano, nitro, halogen, C1C ₆ -alkyl, halo-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio, halo-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ -alkoxy, halogen-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C ₁ -C _6- alkylcarbonyl, C ₁ -C ₆ -alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino;

ζ is an ordinary bond, C (O), C (8) or 8 (O) _P ;

a is 1, 2 or 3;

p represents 0, 1 or 2.

In another embodiment of the first aspect of the invention, the compounds of formula (I) above are compounds wherein

P and O are Ν;

- 5 016912

V represents CK ₈ ;

represents CK ₉ ;

X represents CK ₁₀ ;

Υ represents CK ₁₁ ;

K ₃ , K ₄ and Kb are hydrogen atoms;

K ₈ , K ₉ , K ₁₀ and Κι · each independently of each other, are hydrogen, amino, amido, cyano, nitro, halogen, C ₁ -C ₆ -alkyl, C ₂ -Cb-alkenyl, C ₂ -C _6- alkynyl, C ₃ -C ₇ cycloalkyl, hydroxy-C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, arylthio , C ₁ -C ₆ alkoxy, phenoxy, C1-C6-alkoxy-C1-C6-alkoxy, C3-C7-cycloalkyloxy, halogen-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkylsulfinyl, halogen-C ₁ -C ₆ -alkylsulfinyl, C ₁ -C ₆ alkylsulfonyl, C ₁ -C ₆ -alkylamino, di (C ₁ -C ₆ -alkyl) amino, C ₁ -C ₆ -alkylcarboxy lamin, C ₁ -C ₆ alkylamino-C1-C6-alkoxy, di-C1 -C6 alkylamino-C1 -C6 alkoxy, C1 -C6 alkylamino-C1 -C6 alkyl, di-C1C ₆ -alkylamino-C ₁ -C ₆ -alkyl, amino-C ₁ -C ₆ -alkyl, formyl, HO ₂ C-, C ₁ -C ₆ -alkyl-O ₂ C-, unsubstituted or substituted aryl or unsubstituted or substituted phenoxy, with the result that each of the substituents may be independent of each other and be selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylthio, halogen- C ₁ -C ₆ alkylthio, arylthio, C ₁ -C ₆ alkoxy, halogen-C ₁ -C ₆ alkoxy, C ₁ -C ₆ -alkylcarbonyl, g halogen-C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkylsulfinyl, halogen-C ₁ -C ₆ -alkylsulfinyl, C ₁ -C ₆ -alkylsulfonyl, halogen-C ₁ -C ₆ -alkylsulfonyl;

K ₅ is methyl or C ₁ -C ₃ alkyl;

K ₇ represents hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ C6 alkylthiocarbonyl or unsubstituted or substituted phenyl, in wherein each of the substituents can be independent of each other and be selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ -alkyl, phenyl, phenoxy, C ₁ -C _6- alkylthio, halo-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ -alkoxy, halogen C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl , C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkyl lsulfonyl, halogen-C1-C6 alkylsulfonyl, C1-C6-alkylamino, di (C1-C6) alkylamino;

unsubstituted or substituted hetaryl, in which each of the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, C1-C6 alkyl, halogen-C1-C6-alkyl, C1-C6-alkylthio, halogen-C1-C6-alkylthio, arylthio, C1-C6-alkoxy, halogen-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfonyl C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6) alkylamino; or unsubstituted or substituted naphthyl or quinolyl, in which each of the substituents can be independent of each other and be selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ - alkyl, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ -alkoxy, halogen C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino;

ζ is an ordinary bond, C (O), C (8) or 8 (O) _P ;

a is 1;

p represents 0 or 1.

In yet another embodiment of the first aspect of the invention, the compounds of formula (I) above are compounds wherein

P and O are Ν;

V represents CK ₈ ;

represents CK ₉ ;

X represents CK ₁₀ ;

Υ represents CK ₁₁ ;

K ₈ , K ₉ , K ₁₀ and B _p , each independently of one another, are hydrogen, amino, amido, cyano, nitro, halogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₇ cycloalkyl, hydroxy-C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ alkoxy, phenoxy, C1-C6-alkoxy-C1-C6-alkoxy, C3-C7-cycloalkyloxy, halogen-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C1-C6- alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino, C1-C6-alkylcarboxylamino, C1-C6 alk alkylamino-C1-C6-alkoxy, di-C1-C6-alkylamino-C1-C6-alkoxy, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, amino-C1- C6-alkyl, formyl, HO2C-, C1-C6-alkyl-O2C-, unsubstituted or substituted aryl or unsubstituted or substituted phenoxy, as a result of which each of the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, C1-C6 alkyl, halogen-C1-C6-alkyl, C1-C6 -alkylthio, halogen-C1-C6 -alkylthio, arylthio, C1-C6-alkoxy, halogen-C1-C6-alkoxy, C1-C6- alkylcarbonyl, halogen-C1-C6-alkylcarbonyl, C1-C6-alkylsul inila, halo-C1-C6-alkylsulfinyl, C1-S6alkilsulfonila, halo-C1-S6alkilsulfonila;

K ₃ , K ₄ and K ₆ are hydrogen atoms;

- 6 016912

₅ represents methyl or C1-C3 alkyl;

B ₇ represents hydrogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkylthiocarbonyl or unsubstituted or substituted phenyl, in which each of the substituents can be independent of each other and be selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ -alkyl, phenyl, phenoxy, C ₁ - C ₆ -alkylthio, halo-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ -alkoxy, halogen-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alk ylsulfonyl, halogen-C1-C6 alkylsulfonyl, C ₁ -C ₆ alkylamino, di (C ₁ -C ₆ alkyl) amino;

unsubstituted or substituted hetaryl, in which each of the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, C1-C6 alkyl, halogen-C ₁ -C ₆ alkyl, phenyl, phenoxy, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ -alkoxy, halogen C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C ₁ - C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino;

ζ is C (O) and a is 1.

In yet another embodiment of the first aspect of the invention, the compounds of formula (I) above are compounds wherein

P and O are Ν;

V represents CK ₈ ;

represents CK ₉ ;

X represents CB ₁₀ ;

Υ represents C-B ₁₁ ;

At ₈ , At ₉ , At ₁₀ and Its. each independently from each other, are hydrogen, amino, amido, cyano, nitro, halogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₃ -C ₇ - cycloalkyl, hydroxy-C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ -alkoxy, phenoxy , C1-C6-alkoxy-C1-C6-alkoxy, C3-C7-cycloalkyloxy, halogen-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1 -C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino, C1-C6-alkylcarboxylamino, C1-C6-alkylamino-C1-C6-alk xi, di-C1 -C6 alkylamino-C1 -C6 alkoxy, C1 -C6 alkylamino-C1 -C6 alkyl, _di-C1C-6 alkylamino C ₁ -C ₆ -alkyl, amino-C ₁ -C ₆ -alkyl, formyl, HO ₂ C-, C ₁ -C ₆ -alkyl-O ₂ C-, unsubstituted or substituted aryl or unsubstituted or substituted phenoxy, as a result of which each of the substituents can be independent of each other and be selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, arylthio, С ₁ - C ₆ alkoxy, halogen-C ₁ -C ₆ alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C ₁ - C ₆ alkylsulfinyl, halo-C1-C6-alkylsulfinyl, C1-S6alkilsulfonila, halo-C1-S6alkilsulfonila;

B ₃ , B ₄ and Be are hydrogen atoms;

K ₅ is methyl;

B ₇ represents unsubstituted or substituted phenyl, in which each of the substituents can be independent from each other and be selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ - alkyl, phenyl, phenoxy, C ₁ -C ₆ alkylthio, halogen-C ₁ -C ₆ alkylthio, arylthio, C ₁ -C ₆ alkoxy, halogen-C ₁ -C ₆ alkoxy, C ₁ -C ₆ - alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6-alkyl) amino; unsubstituted or substituted hetaryl, in which each of the substituents can be independently selected from the group consisting of cyano, nitro, halogen, C1-C6 alkyl, halogen-C1-C6-alkyl, C1-C6-alkylthio, halogen-C1- C6-alkylthio, arylthio, C1-C6-alkoxy, halogen C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6-alkylsulfonyl C1-C6 alkylamino; di (C1-C6-alkyl) amino;

ζ is C (O) and a is 1.

In yet another embodiment of the first aspect of the invention, the compounds of formula (I) above are compounds wherein

P and O are Ν;

V represents CK ₈ ;

represents CK ₉ ;

X represents CB ₁₀ ;

Υ represents C-B ₁₁ ;

B ₃ , B ₄ and Kb are hydrogen atoms;

K ₅ represents hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkylthioalkyl, alkyloxyalkyl or alkylsulfonyloxyalkyl;

B ₇ represents unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of alkyl, haloalkyl, phenyl, phenyloxy, alkoxy, halogen

7 016912 nalkoxy, alkylthio, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl;

B ₈ , B ₉ , K ₁₀ and K _p , each independently of one another, are hydrogen, halogen, alkyl, haloalkyl, cyano, alkoxy, haloalkoxy, alkenyl, alkylamino, hydroxyalkyl, formyl, alkylaminoalkyl, dialkylaminoalkyl, aminoalkyl, HO ₂ C-, alkyl-O ₂ C-, formyl, or unsubstituted or substituted phenyl, in which the substituents are alkyl or haloalkyl;

ζ is C (O) and a is 1.

In yet another embodiment of the first aspect of the invention, the compounds of formula (I) above are compounds wherein

P and O are Ν;

V represents CK ₈ ;

represents CK ₉ ;

X represents CK _{| 0} ;

Υ represents CK ₁₁ ;

B ₃ , B ₄ and K ₆ are hydrogen atoms;

₅ represents hydrogen, C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, hydroxy-C ₁ -C ₆ -alkyl, C ₁ -C ₆ alkylthio-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkyloxy-C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkylsulfonyloxy-C ₁ -C ₆ -alkyl;

B ₇ is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of C | -C ₆ -alkyl. halogen-C ₁ -C ₆ -alkyl, phenyl, phenoxy, C ₁ -C ₆ alkoxy, halogen-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, halogen -C ₁ -C ₆ alkylsulfinyl and halogen-C1-C6 alkylsulfonyl;

B ₈ , B ₉ , K ₁₀ and Bn, each independently of one another, are hydrogen, halogen, C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, cyano, C ₁ -C ₆ -alkoxy, halogen-C 1- C6-alkoxy, C1-C6-alkenyl, C1-C6 alkylamino, hydroxy-C1-C6-alkyl, formyl, C1-C6-alkylamino-C1-C6-alkyl, HO2C-, C1-C6-alkyl-O2 or unsubstituted or substituted phenyl wherein the substituents are C ₁ -C ₆ alkyl or haloC ₁ -C ₆ alkyl;

ζ is C (O) and a is 1.

In yet another embodiment of the first aspect of the invention, the compounds of formula (I) above are compounds wherein

P and O are Ν;

Υ represents CK ₈ ;

represents CK ₉ ;

X represents CK _{| 0} ;

Υ represents CK ₁₁ ;

B ₃ , B ₄ and Kb are hydrogen atoms;

₅ represents methyl, ethyl, butyl, Sn ₂ OH, CH ₂ OCH ₃ , CH ₂ 8CH ₃ , CH ₂ O8O ₂ CH ₃ ;

B ₇ represents phenyl substituted with butyl, CP ₃ , phenyl, phenoxy, OCP ₃ , 8CP ₃ , 8OCP ₃ , 8O2CP3;

B ₈ , B ₉ , K ₁₀ and K ₁₁ , each independently of one another, are hydrogen, methyl, CH ^ H ₂ , CH ^ (CH ₃ ) ₂ , vinyl, CH ₂ OH, CH (OH) CH ₂ OH , CO ₂ H, CO ₂ CH ₃ , Py-CP ₃ , P, C1, Br, SR ₃ , OCP ₃ or ΟΝ;

ζ is C (O) and a is 1.

In a second aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

O represents CB ₂ ;

V represents CK ₈ ;

represents CK ₉ ;

X represents CK _{| 0} ;

Υ represents CK ₁₁ ;

B ₂ represents hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkoxy or alkylaminoalkoxy, dialkylaminoalkoxy;

B ₃ , B ₄ and Kb are hydrogen atoms;

₅ represents hydrogen, alkyl or haloalkyl;

K7 is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl;

B ₈ , B ₉ , K ₁₀ and B _p , each independently of one another, are hydrogen, halogen, alkyl, haloalkyl, nitro, amino, amido, alkyl-O ₂ C- or alkylcarbonylamino;

ζ is C (O) and a is 1.

- 8 016912

In another embodiment of the second aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

O represents CK ₂ ;

V represents CK ₈ ;

V represents CK ₉ ;

X represents CK ₁₀ ;

Υ represents CK ₁₁ ;

K ₂ represents hydrogen, halogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, halogen C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkoxy- C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkylamino-C ₁ -C ₆ alkoxy;

In ₃ , K ₄ and Kb are hydrogen atoms;

K ₅ represents hydrogen, C ₁ -C ₆ -alkyl or halogen-C ₁ -C ₆ -alkyl;

K ₇ is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of C | -C ₆ -alkyl. halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, halogen-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ alkylsulfinyl and halogen-C ₁ -C ₆ alkylsulfonyl;

K ₈ , K ₉ , Kyu and K _p , each independently from each other, are hydrogen, halogen, C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, nitro, amino, amido, C ₁ -C _6- alkyl-O ₂ C- or C ₁ -C ₆ -alkylcarbonylamino;

ζ is C (O) and a is 1.

In yet another embodiment of the second aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

O represents CK ₂ ;

V represents CK ₈ ;

V represents CK ₉ ;

X represents CK ₁₀ ;

Υ represents CK ₁₁ ;

K ₂ represents hydrogen, C1, methyl, methoxy, ethoxy, propoxy, butoxy, O (CH ₂ ) ₂ OCH ₃ or O (CH ₂ ) ^ (CH 3) ₂ ;

K3, K4 and K6 are hydrogen atoms;

K5 is methyl;

K ₇ represents phenyl substituted with OSE ₃ , phenoxy or 8CE ₃ ;

K ₈ , K ₉ , K ₁₀ and K _p , each independently of one another, are hydrogen, C1, Br, C ₁ -C ₆ alkyl, CE ₃ , nitro, amino, amido, CO ₂ CH ₃ or ΝΗΟΟίΗ ₃ ;

ζ is C (O) and a is 1.

In a third aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

represents CK ₂ or Ν;

V represents Ν;

V represents CK ₉ ;

X represents CK ₁₀ ;

Υ represents CK ₁₁ ;

K2 represents hydrogen, halogen, alkyl, alkoxy or haloalkoxy;

K3, K4 and K6 are hydrogen atoms;

K5 represents hydrogen, alkyl or haloalkyl;

K ₇ is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl;

K ₉ , K ₁₀ and K ₁₁ , each independently of one another, are hydrogen, halogen, alkyl or haloalkyl;

ζ is C (O) and a is 1.

In another embodiment of the third aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

O represents CK ₂ or Ν;

V represents Ν;

V represents CK ₉ ;

X represents CK ₁₀ ;

- 9 016912

Υ represents C-Kc;

V ₂ represents hydrogen, halogen, _C1-C6 alkyl, _C1-C6 alkoxy or halo _C1-C6 alkoxy;

B ₃ , B ₄ and B ₆ are hydrogen atoms;

₅ represents hydrogen, C ₁ -C ₆ alkyl or halogen-C ₁ -C ₆ alkyl;

B- is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogen-C ₁ C ₆ alkoxy, C ₁ -C ₆ alkylthio, halo-C ₁ -C ₆ alkylthio, halogen-C ₁ -C ₆ alkylsulfinyl and halogen-C ₁ -C ₆ alkylsulfonyl;

Woo. Vu and B ₁₁ , each independently of one another, are hydrogen, halogen, C ₁ -C ₆ -alkyl or halogen-C ₁ -C ₆ -alkyl;

ζ is C (O) and a is 1.

In yet another embodiment of a third aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

O represents CB ₂ or Ν;

V represents Ν;

represents CB ₉ ;

X represents CB ₁₀ ;

Υ represents C-B ₁₁ ;

B ₂ represents hydrogen, C1, Br, methoxy;

B3, B4 and B6 are hydrogen atoms;

B5 is methyl;

B ₇ represents phenyl substituted with OCP ₃ or 8CP ₃ ;

B ₉ , B ₁₀ and B ₁₁ , each independently of one another, are hydrogen, C1, Br or methyl;

ζ is C (O) and a is 1.

In a fourth aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

represents CB ₂ or Ν;

V represents CB ₈ or Ν;

represents CB ₉ ;

X represents CB ₁₀ ;

Υ represents C-B ₁₁ ;

B ₂ represents hydrogen, C1, Br, methyl or methoxy;

B3, B4 and B6 are hydrogen atoms;

₅ represents methyl;

B ₇ represents phenyl optionally substituted with OCP ₃ , 8 CP ₃ or CHPC ₃ ;

B ₈ , B ₉ , B ₁₀ and B ₁₁ , each independently of one another, are H, C1, Br, methyl, CP ₃ or ΟΝ;

ζ is C (O) and a is 1.

In another embodiment of a fourth aspect of the present invention, the compounds of formula (I) above are compounds in which

P represents Ν;

O represents CB ₂ or Ν;

V represents CB ₈ or Ν;

represents CB ₉ ;

X represents CB ₁₀ ;

Υ represents C-B ₁₁ ;

B ₂ represents hydrogen, C1, Br, methyl or methoxy;

B3, B4 and B6 are hydrogen atoms;

B5 is methyl;

B ₇ represents phenyl substituted with OCP ₃ , 8CP ₃ or CHPC ₃ ;

B ₈ represents H, C1, Br, P or ΟΝ;

B ₉ represents H, C1 or Br;

B ₁₀ represents H, C1, Br or CP ₃ ;

B ₁₁ represents H, C1, Br or methyl;

ζ is C (O) and a is 1.

In a fifth aspect of the present invention, the compounds of formula (I) above are

- 10 016912 compounds in which

P represents Ν;

O represents CK ₂ or Ν;

V represents Ν;

V represents CK ₉ ;

X represents CK ₁₀ ;

Υ represents CK _p ;

K ₂ represents hydrogen, C1, Vg or methoxy;

In ₃ , K ₄ and Kb are hydrogen atoms;

K ₅ is methyl;

K ₇ represents phenyl substituted by OCP ₃ or 8CP ₃ ;

K ₉ represents H;

K ₁₀ represents C1 or Br;

K ₁₁ represents H;

ζ is C (O) and a is 1.

Dosage forms and administration in pharmaceutical / veterinary use

Another aspect of the present invention is the preparation of antiparasitic compositions that contain the derivatives of the arylazolo-2-ylcyanoethylamine of the present invention. Such compositions of the present invention may also be in various forms, which include, but are not limited to, oral dosage forms, injectable preparations and local, dermal or subdermal dosage forms. Dosage forms are believed to be administered to animals that are not limited to mammals, birds, and fish. Examples of mammals include, but are not limited to humans, cattle, sheep, goats, llamas, alpacas, pigs, horses, donkeys, dogs, cats and other livestock or pets. Examples of birds include turkeys, chickens, ostriches, and other livestock or poultry.

The composition of the present invention may be in a form suitable for oral administration, for example in the form of a bait (see, for example, US Pat. No. 4,564,631), dietary supplements, lozenges, lozenges, chewable tablets, tablets, hard or soft capsules, emulsions, water or oily suspensions, aqueous or oily solutions, oral moisture-saturated dosage forms, powdered powders or granules, premixes, syrups or elixirs, enteric-soluble dosage forms or pastes. Compositions intended for oral use may be prepared by any method known in the art for the preparation of pharmaceutical compositions, and such compositions may contain one or more agents selected from the group consisting of sweeteners, bitter tastants, flavoring agents, dyes and preservatives, to provide pharmaceutically elegant preparations and preparations with an attractive taste.

Tablets may contain the active ingredient in admixture with non-toxic, pharmaceutically acceptable inert excipients which are suitable for the preparation of tablets. Such inert fillers may, for example, be inert diluents, for example calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating or disintegrating substances, for example corn starch or alginic acid; binding agents, for example starch, gelatin or agarose, and lubricants, for example magnesium stearate, stearic acid or talc, tablets may be uncoated or they may be coated by known techniques to prevent disintegration and adsorption in the gastrointestinal tract and thus to provide prolonged action for a longer period. For example, prolonging materials such as glycerol monostearate or glycerol distearate can be used. They can also be coated according to the technology described in US patent No. 4256108; 4,166,452 and 4,265,874 (incorporated herein by reference) for the manufacture of osmotic therapeutic tablets for controlled excretion.

Dosage forms for oral administration can be hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example calcium carbonate, calcium phosphate or kaolin.

Capsules can also be soft gelatin capsules in which the active ingredient is mixed with water or water-miscible solvents, for example propylene glycol, PEGmi (REG) and ethanol, or with an oil medium, for example peanut oil, liquid paraffin or olive oil.

The compositions of the present invention may also be in the form of oil-water-oil or water-oil-water emulsions. The oil phase may consist of vegetable oil, for example olive oil or peanut oil, or mineral oil, for example liquid paraffin or mixtures thereof. Suitable emulsifying agents may be naturally occurring phospholipids, for example, from soy,

11 016912 lecithin and esters or partial esters derived from fatty acids and hexitol anhydrides, for example sorbitol monooleate, and condensation products of said partial esters with ethylene oxide, such as polyoxyethylene sorbitan monooleate. Emulsions may also contain sweeteners, bitter tastants, flavoring agents and / or preservatives.

In one embodiment of the dosage form, the composition of the present invention is in the form of a microemulsion. Microemulsions are well suited as a liquid vehicle. Microemulsions are systems consisting of four components, including an aqueous phase, an oil phase, a surfactant and a second surfactant. They are transparent and isotropic liquids.

Microemulsions consist of stable dispersions of microdroplets of the aqueous phase in the oil phase or, conversely, microdroplets of the oil phase in the aqueous phase. The sizes of microdrops are less than 200 nm (1000-100000 nm for emulsions). The interfacial film consists of alternating molecules of a surfactant, PA (8L) and molecules of a second surfactant (Co-8L), which, by reducing surface tension, create the possibility for spontaneous formation of a microemulsion.

In one embodiment of the oil phase, the oil phase may be formed from mineral or vegetable oils, from unsaturated polyglycosylated glycerides, or from triglycerides, or alternatively from mixtures of these compounds. In one embodiment of the oil phase, the oil phase consists of triglycerides; in another embodiment of the oil phase, the triglycerides are medium-length triglycerides, for example, C8C1 ₀ caprylic acid / capric acid triglycerides. In another embodiment, the oil phase is presented as a range (% v / v) selected from the group consisting of from about 2 to about 15% v / v .; from about 7 to about 10% v / v and from about 8 to about 9% vol./about. microemulsions.

The aqueous phase includes, for example, water or glycerol derivatives such as propylene glycol, glycol ethers, polyethylene glycols or glycerol. In one embodiment, the implementation of glycol derivatives, the glycol is selected from the group consisting of propylene glycol, diethylene glycol monoethyl ether, dipropylene glycol monoethyl ether, and mixtures thereof. Typically, the proportion of the aqueous phase in the microemulsion is from about 1 to about 4% v / v. Surfactants for microemulsions include diethylene glycol monoethyl ether, dipropylene glycol monoethyl ether, C ₈ -C ₄₀ glycerides modified with polyglycol, or polyglyceryl-6-dioleate. In addition to these surfactants, second surfactants include short chain alcohols, for example ethanol and propanol.

Some compounds are common to the components discussed above, i.e., the aqueous phase, surfactant and second surfactant. However, it is better to use different compounds for each component of the same dosage form within the skill level of the contractor. In one embodiment, for the amount of the main surfactant / second surfactant, the ratio of the second surfactant to the main surfactant is in the range of about 1/7 to about 1/2. In another embodiment, for the amount of the second surfactant, the ratio is in the range of from about 25 to about 75% v / v. the main surfactant and from about 10 to about 55% vol./about. a second surfactant in a microemulsion.

Oily suspensions may be prepared by suspending the active ingredient in a vegetable oil, for example peanut oil, olive oil, sesame oil, or coconut oil, or in mineral oil, for example liquid paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweeteners such as sucrose, saccharin or aspartame, bitter tastants and flavoring agents can be added to give oral preparations an attractive taste. These compositions can be stabilized by the addition of antioxidants, for example ascorbic acid or other known stabilizers.

Aqueous suspensions may contain the active substance in admixture with excipients suitable for the preparation of aqueous suspensions. Such excipients are suspending agents, for example, carboxymethyl cellulose sodium, methyl cellulose, hydroxypropyl methyl cellulose, sodium alginate, polyvinyl pyrrolidone, tragacanth gum and gum arabic; dispersing or moisturizing agents can be naturally occurring phosphatides, for example lecithin or condensation products of alkylene oxide and fatty acids, for example polyoxyethylene stearate or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethenoxycetanol and condensation products of ethylene oxide and non-fatty esters, for example polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fat acids and hexitol anhydrides, for example polyoxyethylene sorbitan monooleate. Aqueous suspensions may also contain one or more stabilizers, for example p-hydroxybenzoic acid ethyl or n-propyl ester or one or more

- 12 016912 dyes, one or more flavoring substances and one or more sweeteners and / or agents with a bitter taste, for example, from those described above.

Dispersed powders and granules suitable for preparing an aqueous suspension by adding water make it possible to use the active ingredient in a mixture with a dispersing or moisturizing agent, a suspending agent and one or more stabilizers. Examples of suitable dispersing or wetting agents are those agents which are already mentioned above. Additional excipients, for example, sweeteners, bitter tastants, flavoring and coloring agents, may also be present.

Formulations of syrups and elixirs are made together with sweeteners, for example glycerin, propylene glycol, sorbitol or sucrose. Such dosage forms may also contain sedatives, stabilizers, flavoring agent (s) and dye (s).

In another embodiment of the present invention, the composition may be in the form of a paste. Examples of embodiments in the form of a paste include, but are not limited to those described in US patent No. 6787342 and 7001889 (each of which is incorporated here by reference). Along with the aryloazol-2-ylcyanomethylamine derivatives of the present invention, the paste may also contain fumed silica; viscosity modifier; carrier; optionally an adsorbent; and optionally a dye, stabilizer, surfactant or preservative agent.

The method of preparation of the dosage form in the form of a paste consists of the following stages:

(a) dissolving or dispersing the aryloazol-2-ylcyanomethylamine derivative in the carrier by mixing;

(b) adding pyrogenic silica to a carrier containing a dissolved aryloazol-2-ylcyanomethylamine derivative until the silica gel is dispersed in the carrier;

(c) allowing the intermediate formed in step (b) to settle for a time sufficient for the air entrained in step (b) to escape; and (b) adding a viscosity modifier to the intermediate by mixing to obtain a uniform paste.

The above steps are illustrative, but not limiting. For example, step (a) may be the last step.

In one embodiment of the dosage form, the dosage form is a paste containing an aryloazol-2-ylcyanomethylamine derivative, fumed silica, viscosity modifier, adsorbent, dye; a hydrophilic carrier such as triacetin, monoglyceride, diglyceride or triglyceride.

The paste may also include, but is not limited to, a viscosity modifier selected from the group consisting of PEG 200, PEG 300, PEG 400, PEG 600, monoethanolamine, triethanolamine, glycerol, propylene glycol, polyoxyethylene (20) sorbitan monooleate (Polysorbate 80 or Teteyee 80 ) and a polyoxamer (e.g. P1itoxic b 81); an adsorbent selected from the group consisting of magnesium carbonate, calcium carbonate, starch, cellulose and its derivatives; a dye selected from the group consisting of titanium dioxide, iron oxide and ΡΌ & C B1ie # 1 A1ittit bake.

The compositions may be in the form of a sterile injectable aqueous or oily suspension. This suspension can be obtained by known methods using the appropriate dispersing or wetting agents mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the suitable vehicles and solvents that can be used are water, Ringer's solution and isotonic sodium chloride solution. Co-solvents, for example ethanol, propylene glycol, glycerol formal or polyethylene glycols, may also be used. Preservative agents, for example phenol or benzyl alcohol, may be used.

In addition, sterile fixed oils are usually used as a solvent or suspending medium. For this purpose any bland fixed oil may be used, including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectable drugs.

Local, skin, and subcutaneous dosage forms may include emulsions, creams, ointments, gels, pastes, powders, shampoos, spot-on dosage forms, ready-to-use dosage forms, spot and suspension solutions, disinfectants solutions and sprays. The local use of a patentable compound or composition comprising at least one patentable compound among the active agents in it, compositions applied in the form of a spot, allows the patentable compound to be absorbed through the skin to achieve somatic levels dispersed in the sebaceous glands or on the surface of the skin reaching a level, penetrating through the hairline. When the compound is dispersed in the sebaceous glands, the latter can act as a reservoir, due to which a prolonging effect can be observed (up to several months). Dosage forms applied as a spot are usually applied in a limited area, which occupies an area different from the total area of the abdomen.

- 13 016912 nogo. In one embodiment of a limited area, the position is between the shoulder joints. In another embodiment, the limited area is a strip, for example, a strip from the head to the tail of the animal.

Dosage forms applied as a spot are described in US Pat. No. 6,010710, incorporated herein by reference. Dosage forms in the form of a stain can be predominantly oily and usually contain a diluent or vehicle and a solvent (eg, an organic solvent) for the active ingredient, if the latter is insoluble in the diluent.

Organic solvents that can be used in the invention include, but are not limited to, acetyl tributyl citrate, fatty acid esters, for example dimethyl ether, adipic acid diisobutyl ether, acetone, acetonitrile, benzyl alcohol, diglycol butyl ether, dimethylacetamide, dimethylformamide, n dipropylene glycol butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene alcohol, propylene glycol, 2-pyrrolidone (e.g. Ν-methylpyrrolidone), diethylene glycol monoethyl ether, ethylene glycol and diethyl phthalate, or a mixture of at least two of these solvents.

When used as a vehicle or diluent, attention should be paid to vegetable oils, such as, but not limited to, soybean oil, peanut oil, castor oil, corn oil, cottonseed oil, olive oil, grape seed oil, sunflower oil, coconut oil etc.; mineral oils such as, but not limited to, liquid paraffin, paraffin, silicone, etc .; aliphatic or cyclic hydrocarbons, or alternatively, for example, medium chain triglycerides (e.g., C ₈ -C ₁₂ ). In another embodiment, an anesthetic and / or lyophilizing agent and / or film-forming agent may be added. One embodiment of an anesthetic and / or lyophilizing agent and / or film-forming agent is to use agents selected from the group consisting of:

(a) polyvinylpyrrolidone, polyvinyl alcohol, copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylated esters of sorbitan, lecithin, sodium carboxymethyl cellulose, silicone oil, oil, for example, containing silanol functional groups or oil 45ν2, (b) anionic surfactants, for example alkali metal stearates, sodium, potassium stearates or a mmonia; calcium stearate, triethanolamine stearate; abietic acid sodium salt; alkyl sulfates (e.g. sodium lauryl sulfate and sodium cetyl sulfate); sodium dodecylbenzenesulfonate; sodium dioctyl sulfosuccinate; fatty acids (e.g., derived from coconut oil), (c) cationic surfactants, e.g., water-soluble quaternary ammonium salts of the formula Ν ⁺ Κ'ΚΚ'Κ, Υ ^- , in which the K radicals are optionally hydroxylated hydrocarbon radicals and Υ ^- is a strong acid anion, for example a halide, sulfate and sulfonate anions; cetyltrimethylammonium bromide is part of the cationic surfactants that can be used, (b) salts of amines of the formula Ν ⁺ ΗΚ'ΗΚ ', in which the K radicals are optionally hydroxylated hydrocarbon radicals; octadecylamine is part of the cationic surfactants that can be used, (e) nonionic surfactants, for example sorbitan esters, which are optionally polyoxyethylated (e.g. polysorbate 80), polyoxyethylated alkyl esters; polyoxypropylated fatty alcohols, for example polyoxypropylene styrene ether, polyethylene glycol stearate, polyoxyethylated castor oil derivatives, polyglycerol esters, polyoxyethylated fatty alcohols, polyoxyethylated fatty acids, ethylene oxide-propylene oxide copolymers, (1) amphoteric surfactants, for example; or (e) a mixture of at least two of these agents.

The solvent is used in proportion to the concentration of the aryloazol-2-yl cyanoethylamine derivative and its solubility in this solvent. Try to find the solvent that has the smallest possible volume. The vehicle compensates for the difference up to 100%.

In one embodiment of the analgesic, the analgesic is used in a ratio selected from the group consisting of 0.1-50 and 0.25-5 vol.%.

In another embodiment, the composition may be in the form of a solution, ready to use, as described in US patent No. 6395765, incorporated herein by reference. In addition to the aryloazol-2-ylcyanoethylamine derivative, the ready-to-use solution may contain a crystallization inhibitor, an organic solvent, and an organic cosolvent.

In one embodiment, the amount of crystallization inhibitor is a crystalline inhibitor.

- 14 016912 lysis can be in a quantitative ratio selected from the group consisting of from about 1 to about 20% (wt./about.) And from about 5 to about 15%. In another embodiment, the amount of crystallization inhibitor corresponds to a sample in which 0.3 ml of a solution containing 10% (w / v) of the aryloazol-2-ylcyanoethylamine derivative in a liquid carrier and 10% of the inhibitor is applied to a glass slide at 20 ° C. and left for 24 hours. Then the glass slide is examined with the naked eye. Suitable inhibitors are those upon the addition of which little is formed (for example, less than ten crystals) or no crystals are formed at all.

The organic solvent has a dielectric constant in the range selected from the group consisting of from about 10-35 and from about 20-30, moreover, the content of the organic solvent in the overall composition is an addition to 100% of the composition; and an organic cosolvent having a boiling point selected from the ranges consisting of temperatures below 100 ° C and below 80 ° C, and having a dielectric constant in the range selected from the group consisting of from about 10-40 and from about 20-30; this cosolvent may be present in the composition in an organic cosolvent / organic solvent system in a mass / mass (M / M) ratio of about 1/15 to 1/2. The solvent is volatile in order to act as a drying promoter, and miscible with water and / or with an organic solvent.

The dosage form may also contain an antioxidant designed to inhibit oxidation in air, and this agent is in a quantitative ratio selected from the range consisting of from about 0.005 to about 1% wt./about. and from about 0.01 to about 0.05%.

Crystallization inhibitors that are applicable to the invention include, but are not limited to:

(a) polyvinyl pyrrolidone, polyvinyl alcohol, a copolymer of vinyl acetate and vinyl pyrrolidone, polyethylene glycol, benzyl alcohol, mannitol, glycerin, sorbitol or a polyoxyethylated sorbitan ester, lecithin or sodium carboxymethyl cellulose; or acrylate, for example methyl acrylate, etc.

(b) anionic surfactants, for example alkali metal stearates (for example, sodium, potassium or ammonium stearates); calcium stearates, triethanolamine stearates; abietic acid sodium salt; alkyl sulfates, which include, but are not limited to, sodium lauryl sulfate and sodium cetyl sulfate; sodium dodecylbenzenesulfonate or sodium dioctyl sulfosuccinate; or fatty acids (e.g. coconut oil), (c) cationic surfactants, e.g. water-soluble quaternary ammonium salts of the formula Ν Ν. Υ ^- in which the K radicals are the same or different from each other, optionally hydroxylated hydrocarbon radicals and Υ ^- is a strong acid anion, for example, a halide, sulfate and sulfonate anions; cetyltrimethylammonium bromide is part of cationic surfactants that can be used;

(b) salts of amines of the formula Ν ^ ΗΚ'ΚΚ ', in which the K radicals are the same or different from each other, optionally hydroxylated hydrocarbon radicals; octadecylamine hydrochloride is one of the cationic surfactants that can be used, (e) nonionic surfactants, for example, optionally polyoxyethylated sorbitan esters, for example polysorbate 80, polyoxyethylated alkyl ether; polyethylene glycol stearate, polyoxyethylated castor oil derivative, polyglycerol esters, polyoxyethylated fatty alcohols, polyoxyethylated fatty acids, ethylene oxide and propylene oxide copolymers, (ί) amphoteric surfactants, for example, substituted by lauryl derivatives of betaine; or (e) a mixture of at least two of these compounds listed in (a) to (£) above.

In one embodiment, crystallization inhibitors use two crystallization inhibitors. Such pairs include, for example, a combination of a polymer-type film-forming agent and a surfactant. These agents are selected from the compounds mentioned above as crystallization inhibitors.

In one embodiment of the film-forming agent, the agents are polymer type substances that include, but are not limited to, polyvinylpyrrolidone brands, polyvinyl alcohols, and vinyl acetate-vinylpyrrolidone copolymers.

In one embodiment, the implementation of surfactants, these substances include, but are not limited to those derived from non-ionic surfactants; in another embodiment of the surfactants, these substances are polyoxyethylated sorbitan esters, and in yet another embodiment of the surfactants, these substances include various types of polysorbate, for example polysorbate 80.

In another embodiment of the present invention, a film-forming agent and a surface

The active substance can be administered in similar or identical amounts within the total amounts of the crystallization inhibitor mentioned elsewhere.

Thus, the pair made with the right choice of the goal of eliminating crystallization on the skin and maintaining the cosmetic appearance of the skin or fur, that is, without a tendency to stick or sticky, despite the high concentration of the active product.

In one embodiment of antioxidants, these agents are those that are conventional in technology and include, but are not limited to, butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, sodium metabisulfite, propyl gallate, sodium thiosulfate, or a mixture of not more than two of them.

Adjuvants of the dosage forms discussed above are well known to specialists in this field of technology and can be purchased in large quantities or obtained by known methods. Such concentrated compositions are usually prepared by simply mixing the components as described above; mainly the starting point is the mixing of the active products in a common solvent, after which other ingredients are added.

The volume used may be on the order of from about 0.3 to about 1 ml. In one embodiment, the volume may be about 0.5 ml, for cats about 0.3 to about 3 ml, for dogs, depending on the weight of the animal.

In another embodiment of the present invention, the use of a spot-on dosage form may also provide a prolonged action and broad spectrum efficacy when the solution is applied to mammals or birds. Dosage forms applied as a spot are provided for topical administration of a concentrated solution, suspension, microemulsion or emulsion for intermittent use on an area on the animal’s body, usually between two shoulder joints (solution applied as a spot).

For dosage forms applied as a spot, the carrier may be a liquid vehicle, as described in US Pat. No. 6,426,333 (incorporated herein by reference), which in one embodiment of the dosage form applied as a spot contains a solvent and a co-solvent, in which the solvent is selected from the group consisting of acetone, acetonitrile, benzyl alcohol, diglycol butyl ether, dimethylacetamide, dimethylformamide, dipropylene glycol n-butyl ether, ethanol, isopropanol, methanol, monoethyl ethylene glycol ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, 2-pyrrolidone (for example, Ν-methylpyrrolidone ether, diethylene diethylene diethylglycol ether, diethylene diethyl glycol ether ; and mixtures of at least two of these solvents; and the co-solvent is selected from the group consisting of absolute ethanol, isopropanol or methanol.

The liquid vehicle may optionally comprise a crystallization inhibitor selected from the group consisting of an anionic surfactant, cationic surfactant, nonionic surfactant, amine salt, amphoteric surfactant or polyvinyl pyrrolidone, polyvinyl alcohols, vinyl acetate copolymers and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylated esters of sorbitan, lecithin, sodium acid salts of carboxymethyl cellulose and acrylates or mixtures of these crystallization inhibitors.

Dosage forms applied as a spot can be prepared by dissolving the active ingredients in pharmaceutical or veterinary vehicles. Alternatively, a spot-on dosage form can be prepared by encapsulating the active ingredients so as to leave the remaining therapeutic agent on the surface of the animal. These dosage forms may vary depending on the weight of the therapeutic agent in a combination depending on the type of host animal to be treated, the severity and type of infection, and body weight of the host.

Dosage forms may contain from about 0.5 mg to about 5 g of the active agent. In one embodiment of the dosage form, the dose is from about 1 to at 500 mg of active agent, usually about 25 mg, about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, approximately 800 mg or approximately 1000 mg.

In one embodiment, the active agent is present in a dosage form at a concentration of about 0.05-10% w / v. In another embodiment of the present invention, the active agent is in a dosage form at a concentration of about 0.1-2% w / v. In yet another embodiment of the present invention, the active agent is in a dosage form at a concentration of about 0.25 to about 1.5% w / v. In yet another embodiment of the present invention, the active agent is in a dosage form at a concentration of about 1% w / v.

Another embodiment of the present invention is directed to a method for treating endopar

- 16 016912 infection in mammals if necessary, which includes the introduction of an effective amount of a compound of this invention.

In one of the options for the treatment of endoparasitic infection, it consists in the fact that the helminth is selected from the group consisting of, but not limited to, Aparocosperma (Aporocosperma), Apocococcus, Apesocot, Axaic, Carpacia, Carpociota, Chocococcus, Chocococcus, Cypococcus SuNsoboShorNogik, SuysoyerNapik, Sta1etok1ottst, I1s1uosai1ik, I1re1a1opeta, P1ruybsht, E | goP1aya, Pgasipsi1ik, EsIposossik, Ep1egoshk, Eaksyu1a, Ebago1bek, Nagopeta, NaetopsNik, Me1ak1gopdu1ik, Moshe / 1a, og №sa, №ta1obpik, №rrok1gopdu1ik, Oekoryadoyittst, OpsNosegsa! Oyeyashcha Ohuipk, Ragasapk, 8sy1k1okota, 81top§u1ik, Taesha, Tohosaga, 81toptopu1o1bek, Tohaksapk, TpsypeIa, Tpsyipk, TpsNok1topuyuik, TpoboShoryotoik, Ipsnepaeg.

In another embodiment of the present invention, the helminth is NaetopsNick sosoyik, Ok1eyad1a ssitsschs1a, Tpsnok1kopduy1k akhe1, Tps1yuk1kopduy.1k s1uy1iogt1k, Soorepa sigise1, no.

Another embodiment of the present invention is directed to a method of treating an ectoparasitic infection in mammals if necessary, which comprises administering an effective amount of a compound of the invention.

In one embodiment of the treatment of ectoparasitic infection, the infecting agents are selected from the group consisting of, but not limited to, fleas, ticks, ticks, mosquitoes, flies, lice, meat flies, and combinations thereof.

Dosage forms and administration for agrochemical use

The compounds of formula (I) or their salts can be used as such or in the form of preparations based on them (dosage forms) in the form of combinations with other pesticidal active substances, such as, for example, insecticides, attractants, sterilizers, acaricides, nematicides, herbicides , fungicides, and together with antidotes, fertilizers and / or growth regulators, for example, as a premix / finished mixture.

Insecticides include, for example, phosphoric acid esters, carbamates, carboxylic acid esters, chlorinated hydrocarbons, phenylureas, substances obtained using microorganisms.

Examples of insecticides that may optionally be mixed include, but are not limited to: phosphoric acid esters, e.g. demethone, demethone-8-methyl, diazinon, dichlorophos, dimethoate, etoate, etoprofos, etrimphos, phenitrotion, fenthion, heptenofas, parathion, parathionomethyl, fosalon, poxime, pyrimiphosethyl, pyrimifosmethyl, profenofosfrosofrosofropofof, trifofosofropofof, protiofosfropofiofosfropofof, trisofosofropofof, trifofosofropofof, trisofosofropofof, trisofosofropofof, trisofosofropofof, trisofosofropofof, trisofosofropofof, trifofosofropofof, trifofosofropofof, trisofosofropofof, trifofosofropofof, trifofosofropofof, trisofosofropofof, trifofosofropofof, trifofosofropofof, triforofosofropofof, triforofosofropofof;

carbamates, for example, aldicarb, bendiocarb, a-2- (1-methylpropyl) phenylmethylcarbamate, butocarboxyme, butoxycarboxymene, carbaryl, carbofuran, carbosulfan, chloroethocarb, isoprocarb, methomyl, oxamyl, pyrimicarbox, promycod, tybicarb, propicarbide;

organosilicon compounds (e.g. dimethyl (phenyl) silylmethyl-3-phenoxybenzyl ethers, e.g. dimethyl (4-ethoxyphenyl) silylmethyl-3-phenoxybenzyl ether) or dimethyl (phenyl) silymethyl-2-phenoxy-6-pyridylmethyl ether, e.g. dimethyl- ( 9-ethoxyphenyl) silylmethyl-2-phenoxy-6-pyridylmethyl ether or [(phenyl) -3- (3-phenoxyphenyl) propyl] dimethylsilane, for example (4-ethoxyphenyl) - [3- (4-fluoro-3- (phenoxyphenyl) ) propyl)] dimethylsilane, silafluofen;

pyrethroids (which are also applicable because of their repellent properties, for example, as a mosquito repellent), for example, allethrin, alfamethrin, bioresmetrin, bifentrin, cycloprotrin, cyfluthirin, decamethrin, cyhalogentrin, cypermethrin, deltamethrin, alpha-cyano-3-phenyl-2- methylbenzyl-2,2-dimethyl-3- (2-chloro-2-trifluoromethylvinyl) cyclopropanecarboxylate, fenpropatrin, fenflutrin, fenvalerate, flucytrinate, flumetrin, fluvalinate, permethrin, resmetrin and tralometrin;

nitroimines and nitromethylene, for example 1 - [(6-chloro-3-pyridinyl) methyl] -4,5-dihydro-Nitro-1Nimidazole-2-amine (imidacloprid), L - [(6-chloro-3-pyridyl) methyl] -H ² -cyano-no-methylacetamide (N1-25);

Abamectin, AC 303, 630 (chlorfenapyr), acephate, acrinathrin, alanycarb, aldoxycarb, aldrin, amitraz, azamethiphos, VasShik 1Nig1pd1epk1k, phosmet, phosphamidon, phosphine, prallethrin, propaphos, propetamphos, protoat, piraklofos, pyrethrin, pyridaben, pyridaphenthion, pyriproxyfen , quinalphos, BH7988, rotenone, sodium fluoride, sodium hexafluorosilicate, sulfotep, sulfuryl fluoride, tar oil, teflubenzuron, teflutrin, temefos, terbufos, tetrachlorvinphos, tetramethrin, O-2-tert-butylpyrimofio-isopropyltropyl-isothiopropyltropyl-isothiopropyltropyl-isothiopropyl-isothropyl-isothiopropyl-isothiopropyl-isothiopropyl-isothiopropyl-isothiopropyl-isothiopropylamino thiometon, tralometrin, triflumuron, trimethacarb, vamidotion, UetysShsht basapl, HMS, xylylcarb, benfuracarb, bensultap, bifentrin, bioallertrin, (8) -cyclopentenyl isomer MEK.-bioalletrin, bromofos, cadromoflofetzof, calcium bromofosphonet, , chlorfenvinphos, chlorfluazuron, chlormefos, chloropicrin, chlorpyrifos, cyanophos, beta-kiflutrin, alfacipermetrin, kiofenotrin, kyromazin, dazomet, EET (DDT), demedon-8-methylsulfone, diafentyuron,

- 17 016912 dialifos, dicrotophos, diflubenzuron, dinoseb, dezoksabenzofos, diazakarb, disulfoton, ΌΝΟ, empenthrin, endosulfan, ΕΡΝ, esfenvalerate, ethiofencarb, ethion, etofenprox, fenobucarb, fenoxycarb, fensulfothion, fipronil, flucycloxuron, flufenprox, flufenoxuron, fonofos, formetanat , formotion, phosmethylan, furatiocarb, heptachlor, hexaflumuron, hydramethylnon, hydrocyanic acid, hydroprene, ΙΡ8Ρ, isazophos, isofenfos, isoprothiolan, isoxathion, iodfenfos, cadetrin, lindanefthanamartamide, maltofam, maltamide, malatefam, maltamide, malatefam, maltamide, malate, maltamide, malate, malate, malate, malate, malate, malate, malate, malate, malate, malate, malate, malate, maltamide, malate, malate, malate, malate, malate, malate, malate, malate, maltamide, malate, maltamide, malatefam isium, bread beetle, methacryphos, methamidophos, methidation, methiocarb, methoprene, methoxychlor, methyl isothiocyanate, metholcarb, mevinphos, monocrotophos, iced, Νβοάίρποη егβοάίρποη £ άί ΝΡ ΝΡ ν, nicotine, phenomethane, methane phenethane, phenethoxymethoxymethoxymethoxymethan .

Other insecticides that may optionally be added to the mixture may also belong to the class of compounds described in US patent No. 7001903.

Fungicides that may optionally be added to the mixture include, but are not limited to:

(1) triazoles, which include azaconazole, propiconazole, tebuconazole, ciproconazole, metconazole, amitrol, azocyclotin, BA8 480E, bitertanol, diphenoconazole, fenbuconazole, fenchlorazole, phenetanil, flucosonazole, imlobutolazole, microfluazolazole, microfluazolazole, microfluazolazolazole, (±) -cis-1- (4-chlorophenyl) -2- (1H-1,2,4-triazol-1-yl) cycloheptanol, tetraconazole, triadimefon, triadimenol, triapentenol, triflumisole, triticonazole, uniconazole, their salts with metals and acid adducts;

(2) imidazoles, which include, but are not limited to, imizalil, pefurazoate, prochlorase, triflumisole, 2- (1-tert-butyl) -1 - (2-chlorophenyl) -3- (1,2,4-triazole -1-yl) propan-2-ol, thiazolecarboxanilide, for example 2 ', 6'-dibromo-2-methyl-4-trifluoromethoxy-4'-trifluoromethyl-1,3-thiazole-5-carboxanilide, 1 imidazolyl-1- (4'-chlorophenoxy) -3,3-dimethylbutan-2-one, their metal salts and acid adducts;

(3) compounds of (E) -2-phenyl-3-methoxyacrylic acid methyl ester, which include, but are not limited to:

(E) -2- [2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy] phenyl] -3-methoxyacrylic acid methyl ester, (E) -2- [2- [6- (2-) methyl ester thioamidophenoxy) pyrimidin-4-yloxy] phenyl] -3-methoxyacrylic acid, (E) -2- [2- [6- (2-fluorophenoxy) pyrimidin-4-yloxy] phenyl] -3-methoxyacrylic acid methyl ester, methyl (E) -2- [2- [6- (2,6-difluorophenoxy) pyrimidin-4-yloxy] phenyl] -3-methoxyacrylic ester; methyl ester (E) -2- [2- [3- (pyrimidine -2-yloxy) phenoxy] phenyl] -3-methoxyacrylic acid, (E) -2- [2- [3- (5-methylpyrimidin-2-yloxy) phenoxy] phenyl] -3-methoxyacrylic acid methyl ester, meth (E) -2- [2- [3- (Phenylsulfonyloxy) phenoxy] phenyl] -3-methoxyacrylic acid ester, (E) -2- [2- [3- (4-nitrophenoxy) phenoxy] phenyl methyl ester] -3-methoxyacrylic acid, (E) -2- [2-phenoxyphenyl] -3-methoxyacrylic acid methyl ester, (E) -2- [2- (3,5-dimethylbenzoyl) pyrrol-1-yl] - methyl ester 3-methoxyacrylic acid, methyl (E) -2- [2- (3-methoxyphenoxy) phenyl] -3-methoxyacrylic acid methyl ester (E) -2- [2- (2-phenylethen-1-yl) phenyl )] - 3-methoxyacrylic acid, (E) -2- [2- (3,5-dichlorophenoxy) pyridin-3-yl] -3-methoxyacrylic acid methyl ester, (E) -2- (2) methyl ester - (3- (1,1,2,2-tetrafluoroethoxy) phenoxy) phenyl) -3-methoxyacrylic acid, (E) -2- (2- [3- (alpha-hydroxybenzyl) phenoxy] phenyl) -3 methyl ester -methoxyacrylic acid, (E) -2- (2- (4-phenoxypyridin-2-yloxy) phenyl) -3-methoxyacrylic acid methyl ester, (E) -2- [2- (3-n-propyloxyphenoxy) methyl ester phenyl] -3-methoxyacrylic acid, (E) -2- [2- (3-isopropyloxyphenoxy) methyl ester phenyl] -3-methoxyacrylic acid, (E) -2- [2- [3- (2-fluorophenoxy) methyl ester ) phenoxy] phenyl] -3-methoxyacrylic acid, (E) -2- [2- [3- (2-ethoxyphenoxy) phenoxy] phenyl] -3-methoxyacrylic acid methyl ester lots, (E) -2- [2- (4-tert-butylpyridin-2-yloxy) phenyl] -3-methoxyacrylic acid methyl ester, (E) -2- [2- [3- (3-cyanophenoxy) methyl ester ) phenoxy] phenyl] -3-methoxyacrylic acid, (E) -2- [2 - [(3-methylpyridin-2-yloxymethyl) phenyl] -3-methoxyacrylic acid methyl ester, (E) -2- [2 - [6- (2-methylphenoxy) pyrimidin-4-yloxy] phenyl] -3-methoxyacrylic acid, (E) -2- [2- (5-bromopyridin-2-yloxymethyl) phenyl] -3-methoxyacrylic acid methyl ester (E) -2- [2- (3- (3-iodopyridin-2-yloxymethyl) phenyl)] -3-methoxyacrylic acid methyl ester, (E) -2- [2- [6- (2- chloropyrid in-3-yloxy) pyrimidin-4-yloxy] phenyl] -3methoxyacrylic acid, (E), (E) -2- [2- (5,6-dimethylpyrazin-2-ylmethyloxyiminomethyl) phenyl] -3methoxyacrylic acid methyl ester,

- 18 016912 methyl ester (E) -2- {2- [6- (6-methylpyridin-2-yloxy) pyrimidin-4-yloxy] phenyl} -3 methoxyacrylic acid, methyl ester (E), (E) -2- {2- (3-methoxyphenyl) methyloxyiminomethyl] phenyl} -3-methoxyacrylic acid, (E) -2- {2- (6- (2-azidophenoxy) pyrimidin-4-yloxy] phenyl} -3-methoxyacrylic acid methyl ester methyl ester (E), (E) -2- {2 - [(6-phenylpyrimidin-4-yl) methyloxyiminomethyl] phenyl} -3 methoxyacrylic acid, methyl ester (E), (E) -2- {2- [ (4-chlorophenyl) methyloxyiminomethyl] phenyl} -3-methoxyacrylic acid, (E) -2- {2- [6- (2-n-propylphenoxy) -1,3,5-triazin-4-yloxy] phen yl} -3-methoxyacrylic acid and methyl ester (E), (E) -2- {2 - [(3-nitrophenyl) methyloxyiminomethyl] phenyl} -3-methoxyacrylic acid;

(4) succinate dehydrogenase inhibitors, which include, but are not limited to:

(a) fenfuram, furcarbanil, cyclafluramide, furmecyclox, sidvax, metsulfovax, pyrocarbolide, hydroxycarboxin, shirlan, mebenil (mepronil), benodanil, flutolanyl (MopsiG);

(b) naphthalene derivatives, for example terbinafine, naphthyne, butenafine, 3-chloro-7- (2-aza-2,7,7trimethyl-oct-3-en-5-in);

(c) sulfenamide, for example dichlorofluanide, tolylfluanide, folpet, fluorofolpet, captan, captofol;

(b) benzimidazole, for example carbendazim, benomyl, furatiocarb, fuberidazole, thiophonate methyl, thiabendazole or their salts;

(f) morpholine derivatives, for example, fenpropiomorph, falimorph, dimethomorph, dodeomorph, aldimorph, fenpropidin and their aryl sulfonates, such as, for example, salts of p-toluenesulfonic acid and pdodecylphenyl sulfonic acid;

!

(e) benzothiazole, for example 2-mercaptobenzothiazole;

(11) benzamide, for example 2,6-dichloro-I- (4-trifluoromethylbenzyl) benzamide;

(ί) boron compounds, for example boric acid, boric acid ester, borax;

(ί) formaldehyde and formaldehyde-releasing compounds, for example, mono (poly) semiformal benzyl alcohol, oxazolidine, hexahydro-8-triazine, метил-methylolchloroacetamide, paraformaldehyde, nitropyrine, oxolinic acid, teclophthalam;

(k) tris-I- (cyclohexyl-diazenium dioxy) aluminum, No. (cyclohexyl-diazenium-dioxy) tributyltin or K salt, bis-I- (cyclohexyl-diazenium-diaxy) copper, Ν-methylisothiazolin-3-one, 5-chloro-methylisothiazolin-3-one, 4 5-dichloro-I-octylisothiazolin-3-one, Ν-octylisothiazolin-3-one, 4,5trimethyleneisothiazolinone, 4,5-benzoisothiazolinone, Ν-methylolchloroacetamide;

(l) aldehydes, for example cinnamaldehyde, formaldehyde, glutaraldehyde, β-bromocarine aldehyde;

(t) thiocyanates, e.g. thiocyanatomethylthiobenzothiazole, methylene bistiocyanate and the like;

(o) quaternary ammonium compounds, for example benzyldimethyltetradecylammonium chloride, benzyldimethyldodecylammonium chloride, didecyldimethylammonium chloride;

(o) iodine derivatives, e.g. diiodomethyl-p-tolylsulfone, 3-iodo-2-propynyl alcohol, formal 4-chlorophenyl-3-iodopropargyl, 3-bromo-2,3-diiod-2-propenylethylcarbamate, 2,3,3 triiodallyl alcohol, 3-bromo-2,3-diiod-2-propenyl alcohol, 3-iodo-2-propynyl-n-butylcarbamate, 3-iodo-2-propynyl-n-hexylcarbamate, 3-iodo-2-propynylcyclohexylcarbamate, 3 iodo-2-propynylphenylcarbamate;

(p) phenol derivatives, for example, tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3,5dimethyl-4-chlorophenol, phenoxyethanol, dichlorophen, o-phenylphenol, m-phenylphenol, p-phenylphenol, and 2benzyl-4-chlorophenol and their salts of alkali metals and alkaline earth metals;

(c) bactericidal substances containing an activated halogen group, for example, chloroacetamide, bronopol, bronidox, tectamer, for example 2-bromo-2-nitro-1,3-propanediol, 2-bromo-4'hydroxyacetophenone, 2,2-dibromo- 3-nitrilopropionamide, 1,2-dibromo-2,4-dicyanobutane, b-bromo-β-nitrostyrene;

(d) pyridine, for example 1-hydroxy-2-pyridinethione (and their Να, Pe, Mn, Ζη salts), tetrachloro-4-methylsulfonylpyridine, pyrimethanol, mepanipyrim, dipyrithione, 1-hydroxy-4-methyl-6- (2,4 4-trimethylpentyl) -2 (1H) -pyridine;

(k) metal soaps, for example, tin naphthalenate, copper naphthalenate, zinc naphthalenate, tin octoate, copper octoate, zinc octoate, tin 2-ethylhexanoate, copper 2-ethylhexanoate, zinc 2-ethylhexanoate, tin oleate, copper oleate, zinc oleate, tin, copper phosphate, zinc phosphate, tin benzoate, copper benzoate and zinc benzoate;

(ΐ) metal salts, e.g. copper hydroxycarbonate, sodium dichromate, potassium dichromate, chromate

- 19 016912 lithium, copper sulfate, copper chloride, copper borate, zinc fluorosilicate, copper fluorosilicate and mixtures thereof with fixatives;

(i) oxides, for example, tributyltin oxide, Cu ₂ O, CuO, ΖηΟ;

(ν) dialkyldithiocarbamates, for example, Να and Ζη salt of dialkyldithiocarbamate, tetramethylthiuram disulfide, potassium метил-methyldithiocarbamate;

(those) nitrile, for example 2,4,5,6-tetrachloroisophthalodinitrile, disodium salt of cyanodithioimidocarbamate;

(x) quinolines, for example 8-hydroxyquinoline and its salts;

(y) hydrochloric acid, 5-hydroxy-2- (5H) -furanone;

(ζ) 4,5-dichlorodithiazolinone, 4,5-benzodithiazolinone, 4,5-trimethylene dithiazolinone, 4,5-dichloro (3H) -1,2-dithiol-3-one, 3,5-dimethyltetrahydro-1,3, 5-thiadiazin-2-thion, No. (2-p-chlorobenzoylethyl) hexaminium chloride, No. hydroxymethyl-Y'-methyldithiocarbamate potassium chloride 2-oxo-2- (4hydroxyphenyl) acetohydroximic acid, phenyl- (2-chlorosiphenyl) - (1,2-dichloro-2cyanovinyl) sulfone;

(aa) Ad-, Ζη- or Cu-containing zeolites, as such or included in polymerizable compounds, or (b) mixtures of several of the above fungicides.

Herbicides that are known from the literature and which can be mentioned, which can be combined with compounds of the formula (I), are, for example, the following active compounds (note: compounds or have a common name in accordance with the requirements of the international standardization organization ([ ^ yes η ^ ζаΐ ^ оη £ og δίαηώπάίζαΐίοη (18О) or named using the chemical name, if it is consistent with the accepted code number):

acetochlor; acifluorfen (sodium); aclonifen; AKN 7088, namely [[[1- [5- [2-chloro-4 (trifluoromethyl) phenoxy] -2-nitrophenyl] -2-methoxyethylidene] amino] oxy] acetic acid and its methyl ester; Alachlor; alloxydim (sodium); ametrine; amicarbazone, amidochlor, amidosulfuron; amitrol; AM8, namely ammonium sulfamate; anilophos; azulam; atrazine; azafenidine; azimsulfuron (ΌΡΧA8947); aziprotrin; a drum; BA8 516 N, namely 5-fluoro-2-phenyl-4H-3,1-benzoxazin-4-one; beflubatamide; benazoline (α-ethyl); benfluranyl; benfuresate; bensulfuron (-methyl); bensulide; bentazone (sodium); benzobicyclone; benzofenap; benzofluoride; benzoylprop (-ethyl); benzthiazuron; bialafos (bilanafos); biphenox; bispiribac (sodium); bromacil; bromobutide; bromphenoxime; bromoxynil; bromuron; buminafos; buzoxinone; butachlor; butafenacil; butamiphos; butenachlor; butidazole; butraline; butroxydim; butylate; kafenstrol (CH-900); carbamide; carfentrazone (-ethyl); caloxidime, SOLA, namely 2-chloro ^ No. di-2-propenacetamide; ί, ΌΕΟ namely 2-chlorallyldiethyldithiocarbamate; chloromethoxyphene; chloramben; chlorazifop (-butyl); chlorobromuron; chlorbufam; chlorfenac; chlorofluorenol (-methyl); chloridazone; chlorimuron (ethyl); chloronitrofen; chlorotoluron; chloroxuron; chlorprofam; chlorosulfuron; chlortal (dimethyl); chlorothiamide; chlorotoluron, quinidone (-methyl or -ethyl), kinmethylin; kinosulfuron; celodime; clefoxidime, clodinafop and its ester derivatives (e.g. clodinafop (propargyl)); clomazone; clomeprop; kloproksidim; clopyralid; clopirasulfuron (-methyl); cloransulam (methyl); cumiluron (1C 940); cyanazine; cycloate; cyclosulfamuron (AC 104); cycloxydim; cycluron; cyhalogenfop and its ester derivatives (for example, butyl ether, ΌΕΗ-112); kiperkvit; cypracin; kiprazole; daimuron; 2,4-Ό; 2,4-EV; dalapon; dazomet, desmedipam; desmetrine; diallate; dicamba; dichlorobenyl; dichloroprop (-P); diclofop and its ester derivatives, for example diclofop (-methyl); diclosulam, diethyl (-ethyl); diphenoxuron; diphenzoquat; diflufenican; diflufenzopyr; dimefuron; dimepiperate; dimethachlor; dimetamethrin; dimethenamide (8AX-582H); dimethenamide (-P); dimethasone, dimethipine; dimexiflam, dimethrasulfuron, dinitramine; dinoseb; dinoterb; diphenamide; dipropertin; diquat; dithiopyr; diuron; ENOS; elginazine (-ethyl); EH 77, namely 5-cyano-1- (1,1dimethylethyl) -Y-methyl-1H-pyrazole-4-carboxamide; endotal; epoprodan, ERTS; esprocarb; etalfluralin; ethametsulfuron (-methyl); ethidimuron; etiosin; it is fumezate; ethoxyphene and its esters, for example phenoxaprop-R and ethyl ester, НС-252, ethoxysulfuron, ethobenzanide (HA 52); P5231, namely Ν [2-chloro-4-fluoro-5- [4- (3-fluoropropyl) -4,5-dihydro-5-oxo-1H-tetrazol-1-yl] phenyl] ethanesulfonamide; phenoprop; phenoxane, fenoxaprop and fenoxaprop-R and their esters, for example fenoxaprop-R-ethyl and ethyl ether fenoxaprop; phenoxydim; fentrazamide; fenuron; flamprop (-methyl or -isopropyl or isopropyl-b); plassulfuron; Florazlam; fluazifop and fluazifop-R and their esters, for example fluazifop-butyl and fluazifop-R-butyl; fluazolate, flucarbazone (sodium); fluchloralin; flufenacet (POE 5043), flufenpyr, flumetsulam; flumeturon; flumicrolac (pentyl); flumioxazine (8482); flumipropine; fluometuron; fluorochloridone, fluorodiphene; fluoroglycophene (-ethyl); flupoxam (ΚΝΑ739); flupropacil (IVGS-4243); fluproanate, flupirsulfuron (methyl or sodium); flurenol (-butyl); fluridone; flurochloride; fluroxypyr (-meptyl); flurprimidol, flurtamon; flutiacet (-methyl); flutiamide (also known as flufenacet); fomesafen; foramsulfone; fosamine; furylazole (МΟN 13900), furyloxyphene; glufosinate (-ammonium); glyphosate (β-isopropylammonium); halosafen; halosulfuron (-methyl) and its esters (e.g. methyl ester, Νί .'-319); halogenxifop and its esters; haloxyphop-R (= K-haloxyphop) and its esters; NS-252 (diphenyl

- 20 016912 ether), hexazinone; imazametabents (methyl); imazametapir; imazamox; impzapic, imazapyr; imazquin and salts such as ammonium salts; imazetametapyr; imazetapir, imazosulfuron; indanophan; iodosulfuron (methyl) - (sodium), ioxynil; isocarbamide; isopropaline; isoproturon; isouron; isoxaben; isoxachlortol; isoxaflutol; isoxapyryphop; carbutylate; lactophen; lenacyl; linuron; MCPA; MRSV; mecoprop; mefenacet; mefluidide; mesosulfuron (-methyl); mesotrione; metam, metamifop, metamitron; metazachlor; metabenzthiazuron; metazole; methoxyphenone; methyldimron; methobenzuron, methobromuron; (8) metholachlor; metosulam (CVE 511); methoxuron; metribucin; metsulfuronmethyl; MK-616; molinate; monalid; monocarbamide dihydrosulfate; monolinuron; monuron; MT 128, namely 6-chloro-L- (3-chloro-2-propenyl) -5methyl-L-phenyl-3-pyridazinamine; MK-5950; namely No. [3-chloro-4- (1-methylethyl) phenyl] -2methylpentanamide; nanoanilide; napropamide; nattalam; NC 310, namely 4- (2,4-dichlorobenzoyl) -1methyl-5-benzyloxypyrazole; neburon; nicosulfuron; nipiraclofen; nitralin; nitrofen; nitrofluorfen; norflurazone; orbencarb; oryzaline; oxadiargil (BP-020630); oxadiazone; oxasulfuron; oxaziclomephone; oxyfluorfen; paraquat; pebulat; pelargonic acid; pendimethalin; penoxulam; pentanochlor, pentoxazone; perfluidone; petoxamide, phenisopam; fenmedipam; picloram; picolinafen; piperophos; piributicarb; pyrifenopbutyl; pretilachlor; primisulfuron (-methyl); procarbazone (sodium); procyazin; prodiamine; profluazole, profluralin; proglinacin (α-ethyl); prometon; promethrin; propaclor; propanyl; propaquizaphop; propazine; propam; vysokochlor; propoxycarbazone (sodium), propisamide; prosulfaline; prosulfocarb; prosulfuron (CCA-152005); prichlor; pyraclonyl, pyraflufen (-ethyl); pyrazolinate; pyrazone; pyruruzene sulfonate (-ethyl); pyrazoxifene; piribenzoxime; piributicarb; pyridafol; pyridate; pyriftalide, pyrimidobac (-methyl); pyritiobac (sodium) (KSh-2031); pyroxolop and its esters (for example, propargyl ether); quinclorac; quinmerac; quinoclamine, quinophop and its ester derivatives; quisalofop and quisalofop-R and their ester derivatives, for example quisalofopethyl; quisalofop-R-tefuryl and ethyl; renriduron; rimsulfuron (ΌΡΧ-Ε 9636); 8,275, namely 2- [4-chloro-2-fluoro-5- (2-propynyloxy) phenyl] -4,5,6,7-tetrahydro-2-indindazole; secbumeton; sethoxydim; Siduron simazine; simethrin; 8106279, namely 2 - [[7- [2-chloro-4 (trifluoromethyl) phenoxy] -2-naphthalenyl] oxy] propionic acid and its methyl ester; sulcotrione; sulfentrazone (RMS-97285, P-6285); sulfazuron; sulfometuron (-methyl); sulfosate (Yu-A0224); sulfosulfuron; TCA; tebutam (GSR-5544); tebutiuron; teraloksidim; terbacil; terbucarb; terbuchlor; terbumeton; terbutylazine; terbutrin; TRN 450, namely N.'Y-diethyl-3- | (2-ethyl-6methylphenyl) sulfonyl] -1H-1,2,4-triazole-1-carboxamide; tenylchlor (Ν8Κ-850); thiafluamide; thiazafluron; thiazapir (Mop-13200); thidiazimine (8Ν-24085); tifensulfuron (-methyl); thiobencarb; thiocarbazyl; thralcoxydim; triallate; trisulfuron; triaziflam; triazophenamide; tribenuron (methyl); 2,3,6 trichlorobenzoic acid (2,3,6-TBA), trichloropyr; tridifan; trietazine; trioxysulfuron (sodium), trifluralin; triflusulfuron and its esters (e.g. methyl ester, ΌΡΧ-66037); trimethuron; tritosulfuron; cytodef; Vernolate L 110547, namely 5-phenoxy-1- [3- (trifluoromethyl) phenyl] 1H-tetrazole; IVN-509; Ό-489; L8 82-556; KPP-300; Νϋ-324; Νϋ-330; KN-218; ΌΡΧ-Ν8189; 8C-0774; OOZhSO-535; pc-8910; ν-53482; PP-600; MVN-001; IN-9201; ET-751; IN-6127; IN-2023 and KSh5996.

Suitable herbicidal antidotes include, but are not limited to, benzaxor, clocvintocet, kiometrinil, kiprosulfamide, dichlormide, dicyclonone, dietholate, fenchlorazole, fenchlorim, flurazole, fluxophenim, furylazole, mefenfenfen, mefenfenfen, mefenfenfen, and mefenfenfen,

Components that can be used as active compounds according to the present invention, in mixed dosage forms, for example, known active compounds that are inhibitors, for example, acetolactate synthase, acetyl coenzyme A carboxylase, P8 I, P8 II, HPPOO, phytoendesaturase, protoporphyrinogen oxidase, glutamine synthetase are involved in the biosynthesis of cellulose, 5-enolpyruvyl chikimate-3-phosphate synthetase. Such compounds, as well as other compounds that can be used, the mechanism of action of which is somewhat unknown or different, are described, for example, in Zheeb Vezeagsy 26, 441-445 (1986) or THe Re811C16e Mapia1, 12 (H ηοη 2000 (below is abbreviated as RM), Tne Vgrzzn Sgor Prgoys1yup SoipsI and 1Ne Voya1 8os. ίίешешеш181818 ((ебебебебебебебебеб (ебебИзз) and in the references cited therein.

The compounds of formula (I) can be formulated in various ways depending on the prevailing biological and / or physico-chemical parameters. Examples of possible dosage forms that are suitable are wettable powders (HF), water soluble powders (8P), water soluble concentrates, emulsifiable concentrates (EC), emulsions (HF), for example, oil-in-water and water-in-oil emulsions sprayable solutions, suspension concentrates (8C), dispersions based on oil or water, solutions that are mixed with oil, capsule suspensions (C8), pulverulent preparations (TS), seed treatment products, granules for spreading and applying to the soil, granules (CB) in the form of ikrogranul, spray granules, coated granules and absorbing granules, water dispersible granules (LGL), water soluble granules (8C), υΕν formulations, microcapsules and waxes.

The solid forms of the compounds of formula (I) can be obtained by methods known in the art, for example Vugp e! A1 ... Bs.,

- 21 016912 (1999); S1ikkeg s1 a1., Sguk1a1 81gis1ige Apaukuk - A Rpteg, 2pb Εάίίίοη, OhGogb IpAegkyu Rgekk, (1985).

Said dosage forms can be prepared as such, for example, by mixing the active compounds with at least one solvent or diluent, emulsifier, dispersant and / or binder or fixative, water repellent and optionally one or more dehydrating agents, UV stabilizer, dye, pigment and other manufacturing additives.

These types of specific dosage forms are generally known and described, for example, in \\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\;,, 7, S. Naikeg Ve ^ 1ad, Mischa, 41st 41οη 1986; \ U; De νaη Va1keηiu ^ d, Reqi ^ e Egtyiayopk, Magse1 Eekkeg, Ν.Υ., 1973; K. Mayepk, 8th Ogutd Na ^ Loook, 3τά Εά. 1979, S. Сοοάν ^ η Είά. L0 ^ op.

The necessary additives to dosage forms, such as inert materials, surfactants, solvents and other additives, are also known and described, for example, in Wahlct, Naööök Ш Shkössye eik1 OPiegik; e11 Ν.Ι; Η. V. Olriep, ChrIgsDisiop S ^ e, 2πά Εά., SchegkDepse, Ν.Υ. 1963; MsS’sSsjeop'k Oe1egdep1k; · ιπά WtiYPegk Appia1, MS Pu1. Co., K ^ άdeνοοά Ν.Ι; 81k1eu; · ιπά Vοοά. Εηсус1οреά ^ а о О 8шГасе Айле АдеШк, Сет. Pb1. With. yu., Ν.Υ. 1964; 8bgGeSiGe ^ yasiepakSche Αίyu1еηοx ^ άаάάикίе [8шГасе-ас1Ае е1йу1епе οx ^ άе аάάисίκ], \ У1кк. Vе ^ 1addekdek11., 8ishdag1 1976; Ushpaskeg-Kisy1eg, Syepiksie Tesipo1od1e [Sjetuua1 Tesipo1od], νο1. 7, S. Naikeg Wagg-sch Mishs, 41st Εά. 1986.

Wettable powders are preparations that are evenly distributed in water and which, along with the compounds of formula (I) also contain ionic and / or nonionic surfactants (wetting agents, dispersing agents), for example polyoxyethylated alkyl phenols, polyoxyethylated fatty alcohols, polyoxyethylated fatty amines , fatty alcohol and polyglycol ether sulfates, alkanesulfonates or alkylbenzenesulfonates, sodium lignosulfonate, 2,2'-dinaphthylmethane-6,6'-sodium disulfonate, dibutylnaphthalenesulfon sodium or sodium oleoyl methyl taurinate, as well as a diluent or inert compound. In order to obtain wettable powders, the compounds of formula (I), for example, are ground finely in conventional devices, for example, hammer mills, sand mills and pneumatic mills, and mixed with the additives to the dosage forms both simultaneously and thereafter.

Emulsifiable concentrates are obtained, for example, by dissolving the compounds of formula (I) in an organic solvent, for example, butanol, cyclohexanone, dimethylmethylformamide, xylene or also high boiling aromatics or hydrocarbons or mixtures thereof by adding one or more ionic or nonionic surfactants (emulsifiers). The emulsifiers that can be used are, for example, calcium salts of alkylarylsulfonic acids, such as the calcium salt of dodecylbenzenesulfonate or nonionic emulsifiers, for example polyglycol fatty acid esters, alkylaryl polyglycol ethers, polyglycol fatty alcohol esters, polyethylene oxide / ethylene esters condensates sorbitan, such as esters of sorbitan with fatty acids or esters of polyoxyethylene with sorbitan, for example esters of polyoxyethylene sorbitan with fatty acids.

Powdery preparations are obtained by grinding the active compound together with finely ground solids, for example talc or natural clays, for example kaolin, bentonite or pyrophyllite or diatomaceous earth.

The suspension concentrates may be based on water or oil. They can be obtained, for example, by wet grinding using commercially available ball mills, if appropriate, with the addition of surfactants, as mentioned above, for example, in the case of other types of dosage forms.

Emulsions, for example oil-in-water emulsions (Εν), can be obtained, for example, using agitators, colloidal mills and / or static mixtures using organic solvents and, if appropriate, surfactants, as they are already mentioned above, for example, in the case of other types of dosage forms.

Granules can be obtained either by spraying the compounds of formula (I) on an adsorbing granular inert material or by applying concentrates of active compounds to the surface of carriers, for example sand, kaolinites or granular inert material, using binders, for example polyvinyl alcohol, sodium polyacrylate, or as an alternative to mineral oils . Suitable active compounds can also be granulated in a manner customary to obtain fertilizer granules, if appropriate, in a mixture with fertilizers.

Water-dispersible granules are generally prepared by conventional methods such as spray drying, fluidized bed granulation, disk granulation, mixing in high speed mixers and extrusion in the absence of a solid inert material. For disk granules, fluidized-bed granules, extruder and spray granules, see, for example, the methods in 8gau-Egutd NagDoc 3tά eά. 1979, S. Сοοάν ^ η Είά., GodDop; Ι.Ε. Wgo 147 sneakers .; Reggu'k Syetua1 Εηд ^ ηе ^ 'к Na ^ Loook, 5L Εά., MsGa ^ -NS, No. \ ν Wogk, 1973, p. 8-57.

- 22 016912

In general, agrochemical preparations contain compounds of formula (I) in a range selected from the group consisting of from about 0.1 to about 99 wt.% And from about 0.1 to about 95 wt.%.

The concentration of the compounds of formula (I) in wettable powders is, for example, from about 10 to about 90 wt.%, With the remaining up to 100 wt.% Consisting of the usual components of the dosage form. In the case of emulsifiable concentrates, the concentration of the compounds of formula (I) can reach ranges selected from the group consisting of from about 1% to about 90% and from about 5% to about 80 wt.%. Dosage forms in the form of a powdered preparation are usually in the range selected from the group consisting of from about 1 to 30% by weight of compounds of formula (I) and from about 5 to about 20% by weight of compounds of formula (I). Sprayable solutions are in the range selected from the group consisting of from about 0.05 to about 80% by weight of compounds of formula (I) and from about 2 to about 50% by weight of compounds of formula (I). In the case of water-dispersible granules, the content of the compound of formula (I) partially depends on the form in which the compounds of formula (I) are: in liquid or solid form and in what form the auxiliary agents, fillers, etc., are used in granulation. Water-dispersible granules, for example, are in the range selected from the group consisting of from about 1 to about 95% and from about 10 to about 80 wt.%.

In addition, dosage forms of the said compounds of formula (I) contain, if appropriate, adhesives, humectants, dispersants, emulsifiers, penetrants, preservatives, antifreezes, solvents, fillers, carriers, colorants, defoamers, vaporization inhibitors, pH regulators and regulators viscosity, which are usually used in each case.

The mixtures according to the present invention can be applied through the soil or at the stage of pre-emergence or post-emergence treatment. Mixtures according to the present invention can also be applied through foliage. The mixtures according to the present invention can be used for seed treatment. You can also make the mixture according to the present invention through an irrigation system, for example through irrigation water.

Other active agents for pharmaceutical / veterinary use

Additional pharmaceutically, pesticidal or veterinarily active ingredients, which include, but are not limited to, parasite kills, including acaricides, anthelmintic drugs, endectocides and insecticides, may also be added to the compositions of the present invention. Antiparasitic substances may include both ectoparasitic and endoparasitic agents. Veterinary pharmaceutical agents are well known in the art (see e.g. 9111 Εάίΐίοη, (March 1, 2005)) and include, but are not limited to, acarbose, acepromazine maleate, acetaminophen, acetazolamide, sodium acetazolamide, acetic acid, acetohydroxamic acid, acetylcysteine, acytretin, acyclovir, albutrolisole, albutenolis, albendolzene, albendolzene, alprazolam, altrenogest, amantadine HC1, amikacin sulfate , aminocaproic acid, aminopentamide hydrosulfate, aminophylline / theophylline, amiodarone HC1, amitrac, amitriptyline HC1, amlodipine benzylate, ammonium chloride, ammonium molybdenate, amoxillin, clavulanate, an aminocillin, aminocillinum, aminocillin, lipoxychlorin, aminocillin, lipoxychlorin, aminocillin, lipoxychlorin, aminocillin, lipoxychloride, aminocillin, aminocillin, lipoxychlorin, aminocillin, aminocillin, aminocillin, ), antivenin, apomorphion HC1, apramycin sulfate, ascorbic acid, asparaginase, aspirin, atenolol, atipamezole HC1, atracurium bezylate, atropinsulfate, aurnofin, aurothioglucose, azaperone, azathioprine, baclofeni, turate, benazepril HC1, betamethasone, betanechol chloride, bisacodyl, bismuthsubsalicylate, bleomycin sulfate, boldenone undecylenate, bromide, bromocriptine mesylate, budenoside, buprenorphine HC1, caprolin calcinolitanzincolantene calcitolnosolitanzolitinboltsinolantzolitanzolitanbolizin carboplatin, carnitine, carprofen, carvedilol, kefadroxil, kefazolin sodium, kefixime, kefoperazone sodium, kefotaxime sodium, disodium salt of kefotetan, kefoxitin sodium, kefpodoximproxetil, ceftazidime, kefthiofur sodium, kefthiofur HC1, kefthiaxone sodium, cephalexin, cephalosporin, kefarinin, charcoal (activated), chlorambucil, chloramphenicol, chlordiazepoxide, chlordiazepoxide +/- clindinium bromide, chlorpheniraminodinormonorodinormonorodinormonorodinamonorodinamonorodinamonorodinamonorodinamonorodinomonorodinomonorodinomonorodinomonorodinomonorodinomonorodinomonorodinomonorodinormonetorinprominodinoronetraminodinoronetaminodinorodinraminotronodine , cimetidine, ciprofloxacin, cisapride, cisplatin, citric acid salt, clarithromycin, clemastine fumarate, clenbuterol HC1, clindamycin, clofazimine, clomipramine HC1, clonazepam, clonidine, cloprostenol sodium, disodium azepate, clorsulon, cloxacillin, codeine phosphate, coltsikhin, corticotropin (ACTH), cosintropine, cyclophosphamide, cyclosporine, cyproheptadine HC1, cytarabine, dacarbazine, dactinomycetin decindecindecindecindecindecindecindecindecindecindecin todatefin diacdin dodecin daphthenacetate , desmopressin acetate, deoxycorticosterone pivalate, detomidine HC1, dexamethasone, dexpanthenol, dexraazoxane, dextran, diazepam, diazoxide (oral), dichlorfenamide, dichlorvos, diclofenac sodium, dicloxaline, diethyl dicylbicamide itethylsilbestrol (ΌΕ8), difloxacin HC1, digoxin, dihydrotachysterol (ONT), diltiazem HC1, dimen-23016912 hydrinate, dimecaptol / VL, dimethyl sulfoxide, dinoprosttromethamine diphenylhydramine Hcdisoptamide di-dimethylphosphate di-di doramectin, doxapram HC1, doxepin HC1, doxorubicin HC1, doxycycline, edetate calcium disodium salt, calcium salt ΕΌΤΆ, edrofoniyhlorid, enapril / enaprilat, enoksaparin sodium enrofloksazin, efedrinsulfat, epinephrine, epoetin / erythropoietin, eprinomectin, epsis prantel, erythromycin, esmolol HC1, estradiolkipionate, ethacrylic acid / ethacrinate sodium, ethanol (alcohol), sodium ethidronate, ethodolac, etomidate, efthanasia agent / pentobarbital, famotidine, fatty acid (essential phenamebenthol, omega-phenol, omega iron, filgrastim, finasteride, finpronil, florfenicol, fluconazole, flucytosine, flucrocortisone acetate, flumazenil, flumethasone, flunixinmeglumin, flufluorouracil (5-UI), fluoxetine, fluticasone propionflumetholumfufolefolate, 4, fluticasufinformate, 4 flufizufemone, flufazufolomene, 4, apentine, gemcitabine HCL, gentamicin sulfate, glimepiride, glipizide, glucagon, glucocorticoid agent, glucosamine / chondroitin sulfate, glutamine, glyburide, glycerol (oral), glycopyrrologene, hemelobulinogene, guineufluginogene, gu animal starch, sodium hyaluronate, hydrazoline HC1, hydrochlorothiazide, hydrocodonitartrate, hydrocortisone, hydromorphone, hydroxyurea, hydroxyzine, ifosfamide, imidacloprid, imidocarbidipropinate, impenem sodium sodium, imipraminamine, at, insulin, alpha-2a interferon (recombinant person), iodide (sodium / potassium), ipecacuanu (syrup), sodium iodate, iron dextran, isofuran, isoproterenol HC1, isotretinoin, isoxssurpin HC1, itraconazole, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermectin, ivermethine, HC1, ketoconazole, ketoprofen, ketorolactromethamine, lactulose, leuprolia, levamisole, levetiracetam, levothyroxine sodium, lidocaine HC1, lincomycetin HC1, lyiotironin sodium, lisinopril, lominecin, luminicin, marfenclin, mucinlofen, mucinlofen, mucinlofen, mucinlofen, mucinlofen, mucinlofen, mucinlofen, mucinlorin, mucinlofen, mucinolyn, mucinlofen, mucinolin, mucinlofen, mucinlofen, mucinolignon, mucinlorin, mucinlorin, mucinlofen , meclofenamic acid, medeto Idin HC1, medium chain triglycerides, medroxyprogesterone acetate, megestrol acetate, melarsomin, melatonin, meloksikan, melphalan, meperidine HC1, mercaptopurine, meropenem, metformin HC1, methadone HC1, methazolamide, metenaminmandelat / hippurate, methimazole, methionine, methocarbamol, sodium methohexital, methotrexate, methoxyflurane, methylene blue, metiphenidate, methylprednisolone, metoclopramide HC1, metoprolol, metronidaxol, mexiletin HC1, mibolerlon, midazole HC1, milbemycinoxim, mineral oil, minocycline HC1, misoprostol, mitotan, mitoxantrone HC1, moranteltitrate, morphine sulfate, moxidectin, naloxone HC1, mandrolonone decanoate, naproxen, a drug analgesic agonist (opiate), neomycin sulfate, neostigmine, niacinamide, nitazoxanide, nitro nitrinoidinosin nitroin nitroin nitroin nitroin nitroin nitroin nitroin nitroin nitroin nitroin nitroin nitroin nitroside nitroin nitroin nitroside nitroin nitroside nitroin nitroside nitroin nitroside nitroin nitroside nitroin nitroin nitroside nitroin nitroside nitroin nitroside nitroin nitroside nitroin nitroside nitroin nitroside nitroin nitroin nitrosulfonate , omeprozole, ondansetron, opiate antidiarrheal opiate, orbifloxazine, sodium oxacillin, oxazepam, oxfendazole, oxybutynin chloride, oxymorphone HC1, oxytetracycline, oxytocin, pamidronate disodium salt, pansiliplase y pankuroniybromid, paramomitsinsulfat, parozetin HC1, penicillamine, penicillin, general information, penicillin G, potassium salt of penicillin V, pentazocine, pentobarbital, sodium pentosan polysulfate, pentoxifylline, pergolidmezilat, phenobarbitone, phenoxybenzamine HC1, phenylbutazone, phenylephrine HC1, phenylpropanolamine HC1, phenytoin sodium , pheromone, parenteral phosphate, phytonadione / vitamin K-1, pimobendan, piperazine, pirlimycin HCl, piroxicam, polysulfonated glycosaminoglucan, ponazuril, potassium chloride, pralidoximchloride, praziquantel b, prazosin HC1, prednisolone / prednisone, primidone, procainamide HC1, procarbazine HC1, prochlorperazine, propantelinbromid, propionibakteriynuyu akneformnuyu injection, propofol, propranolol HC1, protamine sulfate, pseudoephedrine HC1, a hydrophilic mukilloid psyllium, pirantlpamoat, piridostigminbromid, pirilaminmaleat, pyrimethamine, quinacrine HC1, quinidine, ranitidine HC1, rifampin, δ-adenosylmethionine (8LMe), saline / hyperosmotic laxative; selamectin, selegiline HC1 / 1-deprenyl, sertraline HC1, sevelamer HC1, sevoflurane, silymarin / milk thistle, sodium bicarbonate, sodium polystyrenesulfonate, sodium stibogluconate, sodium sulfate, sodium thiosulfate, somatotropin, sotalolcinolton, spoltinolone spolnocolone, spoltinolone spolconolone, spoltinolone spolconol, spolincolnolone streptozokine, succimmer, succinylcholine chloride, sucralfate, sulfentanyl citrate, sodium sulfachloropyridazine, sulfadiazine / trimethoprim, sulfamethoxazole / trimethoprim, sulfadimentoxin, sulfadimentoxin / ormetoprim, sulfasalazin, taurine, taurine , terbinaflin HC1, terbutaline sulfate, testosterone, tetracycline HC1, thiabendazole, thiacetarsamide sodium, thiamine HC1, thioguanine, thiopental sodium, thiotepin, thyrotropin, thiamulin, disodium salt of ticarcillin, tyletamine Hclin tinzincin toxin tinpinolcin tincin tinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolin tinpinolyncinolin tinpinolin tinpinolin tinpinolin tinpinolin HC1, telfenamic acid, topiramate, tramadol HC1, trimkilononacetonid, tridentin HC1, trilostane, trimepraxintartrate / prednisolone, tripelinamine HC1, tylosin, urdosil, valproic acid, vanadium, vancominophen mils HC1 vinblastinsulfat, vincristine sulfate, vitamin E / selenium, sodium warfarin, xylazine HC1, yohimbine HC1, zafirlukast, zidovudine (ΑΖΤ), zinc acetate / zinc sulfate, zonisamide, and mixtures thereof.

In one embodiment of the present invention, other arylpyrazole derivatives, for example phenylpyrazoles, as described above in the Background section (e.g. fipronil, pyriprol), are known in the art and are suitable for coupling with the aryloazole-2ylcyanoethylamine derivatives of the present invention. Examples of such aryloazole derivatives include,

- 24 016912 but is not limited to those described in US patent No. 6001384; 6010710; 6,083,519; 6,096,329; 6174540; 6685954 and 6998131, each of which belongs to Mepa1, Yb., ΩπΙπίΠ, CA.

In another embodiment of the present invention, nodulisporic acid and its derivatives (a class of known acaricidal, anthelmintic, antiparasitic and insecticidal agents) can be added to the compositions of the present invention. These compounds are used to treat or prevent infections in humans and animals and are described, for example, in US Pat. for example, those described in the literature cited above.

In another embodiment of the present invention, one or more macrocyclic lactones that act as acaricidal, anthelmintic and insecticidal agents may be added to the compositions of the present invention.

Macrocyclic lactones also include, but are not limited to, avermectin, for example, abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin and milbemycini, for example milbemectin, milbemycin нем, madectin and modectin. Also included are 5-oxo and 5-hydroxy derivatives of said avermectins and milbemectins. Examples of combinations of arylpyrazole compounds with macrocyclic lactones include, but are not limited to those described in US Pat. Nos. 6,426,333; 6,482,425; 6962713 and 6998131 - each of which belongs to Mepa1, Yb., EuSHI, S.A.

Derivatives of macrocyclic lactones are known in the art and can be obtained on an industrial scale or by synthetic methods known in the art. Reference is made to the widely available technical and commercial literature. For avermectins, ivermectin, and abamectin, one can refer, for example, to the work Chttebnb apb Abatesbp, 1989, M.N. Exeb apb Η. ΜΐΌζίΚ ^ 1Shat S. Satreb11, bkbb8fffdeg Vе ^ 1ad, Masgosusys basupeh ίη Aprahbas Thégaru, 2002, bv 1. Vе ^ с ^ иу88е and B.8. Vete, published by CAV1 RiKypd or A1bet8s1yupd e! a1. (1981) Auegtesbpk 81gns1ige Pe! Egtshayop, 1. At. Eat. 8os, 103, 4216-4221. For doramectin, you can ask for help at 'Noeppagu Ragagaogoogo, νοί. 49, No. 1, 1i1u, 1993, 5-15. For milbemycin, reference can be made, in particular, to N.E. e! A1., 1986, Integrated Appb Mbustustk, No. 11. Rgob. Ver., 3, 87-121, MGs№k N. e! A1., 1983, 8n111ch5 oG Mbjötust Ggot Awe ^ tesn ^ η8, Tejebobop Lei., 24, 5333-5336, U.S. Patent Nos. 4,134,973 and EP 0677054.

Macrocyclic lactones are either natural products, or they are their semi-synthetic derivatives. The structures of avermectins and milbemycins are closely related, for example, by the joint use of the complex of the 16-membered cycle of macrocyclic lactone; there is no glycoside fragment of avermectins in milbemycins. Natural avermectin products are disclosed in US Pat. No. 4,310,519 A1bega-8bbbbg e! a1. and derivatives of 22,23-dihydroavermectin are disclosed in CbA1a e! a1. US Pat. No. 4,199,569. Qiapo, US Pat. No. 4,468,390, Weitgu e! A1., US patent No. 5824653, EP 0007812 A1, description of the patent and.K. 1390336, EP 0002916 and, in particular, the patent of New Zealand (Apsage) No. 237086. The naturally occurring milbemycin is described in Aok1 e! A1., U.S. Patent No. 3,950,360, and also in various references cited in Thie Megsk 1pbekh 12 (11 eb., 8. Viba ^ agr Eb., Megsk & Co., 1ps. ^ biebose 81a11op, No.begue (1996). Latidectin is described in Sulfuric acidum, Anthropogenicum, Anthracidum,  , UNO Aegis 1Hogta!, Un, νο1. 17, No. 4, p. 263286, (2003). Semi-synthetic compounds of these classes are well known. this technology and are described, for example, in US patent No. 5077308, US patent No. 4859657, US patent No. 4963582, US patent No. 4855317, US patent No. 4871719, US patent No. 4874749, US patent No. 4427663, US patent No. 43105 19, US patent No. 4199569, US patent No. 5055596, US patent No. 4973711, US patent No. 4978677, US patent No. 4920148 and EP 0667054.

In another embodiment of the present invention, compounds of the class of acaricides or insecticides known as growth regulators (1CB§) can also be added to the compositions of the present invention. Compounds belonging to this group are well known to practitioners and represent a wide range of compounds of various chemical classes. The action of all such compounds is to counteract the development or growth of insect pests. Insect growth regulators are described, for example, in US Pat. No. 3,748,356; US patent No. 3818047; U.S. Patent No. 4,225,598; US patent No. 4798837; US patent No. 4751225, EP 0179022 or I.K. 2140010, as well as U.S. Patent Nos. 6,096,329 and 6,685954 (both of which are owned by Mepa1Bi, Pi1i (L, CA). Examples of 1CB§ suitable for use include, but are not limited to, methoprene, pyriproxifene, hydroprene, cyromazine, fluazuron, lufenuron, novaluron, pyrethroids, formamidines and 1- (2,6-difluorobenzoyl) -3- (2-fluoro-4- (trifluoromethyl) phenylurea.

An anthelmintic agent that can be combined with a compound of the present invention to obtain a composition may relate to benzene disulfonamide derivatives, which include, but are not limited to, clorsulon; or anti-cestic agents, which include, but are not limited to, praziquantel, pyrantel, or morantel.

An antiparasitic agent that can be combined with a compound of the present invention for the purpose of

- 25 016912 irradiation of the composition, may relate to biologically active peptides or proteins, including, but not limited to, depsipeptides, the effect of which is the implementation of neuromuscular contact stimulation of presynaptic receptors belonging to the family of secretin receptors, leading to paralysis and death of parasites. In one embodiment of the depsipeptide, the depsipeptide is emodepside.

An insecticidal agent that can be combined with a compound of the present invention to obtain a composition may be spinosin (e.g., spinosad) or substituted pyridylmethyl derivatives, e.g. imidacloprid. Agents of this class are described above, for example, in US Pat. No. 4,742,060 or in EP 0892060. A practitioner should, within the level of competence, decide which individual compound can be used to treat a particular insect infection. For endoparasites, parasite killing agents that can be combined include, but are not limited to, pyrantel, morantel, benzimidazole (including albendazole, cambendazole, thiabendazole, fenbendazole, febantel, oxfendazole, oxybendazole, triclabendazole, no mebendazole, mebendazole, mebendazole, mebendazole, mebendazole, mebendazole , closantel, ratofoxanide, nitroxinyl, disophenol and papracherquamide. For ectoparasites, insecticides that can be combined also include, but are not limited to, pyrethroids, organophosphates, and a neonicotinoid, such as imidaclopid, as well as compounds such as metaflumisone, amitrace, and ryanodine receptor antagonists.

When appropriate, the anthelmintic, antiparasitic and insecticidal agent may also be selected from the group of compounds described above as suitable for agrochemical use.

In most cases, an additional pesticidal agent is included in a dose of from about 0.1 to about 10 μg. In one embodiment of the invention, the additional pesticidal agent is included in a dose of from about 1 to about 10 μg. In another embodiment of the present invention, the additional pesticidal agent comprises in a dose of from about 5 to about 200 μg / kg of animal weight. In yet another embodiment of the present invention, the additional pesticidal agent is included in a dose of from about 0.1 to about 10 μg / kg of animal weight. In yet another embodiment of the present invention, the additional pesticidal agent is included in a dose of from about 0.5 to about 50 μg / kg.

The weight ratios of the aryloazol-2-ylcyanoethylamine derivative and the additional pesticidal agent are, for example, in the range of from about 5/1 to about 10000/1. However, a mid-level specialist is able to select the appropriate ratio of the aryloazole-2ylcyanoethylamine derivative and the additional pesticidal agent for the intended host and its use.

Another aspect of the present invention is a process for preparing the aryloazole-2ylcyanoethylamine derivatives of the present invention.

Examples

All temperatures are in degrees Celsius; room temperature means a range of 20 to 25 ° C. Reagents are obtained from commercial information sources or obtained using the procedures described in the literature.

ISM (DXM) = dichloromethane

TUE (THF) = tetrahydrofuran

MeOH = methanol

EUN (EON) = ethanol

EA (EA) = ethyl acetate

ΌΜΕ (DMF) = dimethylformamide

Ason (UK) = acetic acid

TEL (TFA) = trifluoroacetic acid

TEA (TEA) = triethylamine

ΌΙΕΑ (DIEA) = diisopropylethylamine

Proton and fluorine magnetic resonance spectra (Ή NMR and ¹⁹ Е NMR, respectively) are recorded on a ναπαη ΙΝΟνΑ NMR spectrometer [400 MHz (1Н) or 500 MHz (1Н) and 377 MHz ( ¹⁹ Е)]. All spectra are recorded in the above solvents. Chemical shifts are given in ppm. relative to tetramethylsilane (TM8), assigned to the residual proton peak of the corresponding solvent for ¹ H NMR. The proton-proton splitting constants are given in Hertz (Hz).

LC-MS spectra are obtained either using the TNegtoPpsdap OA M8 Ε8Ε instrument, using a Reeyoteie Adia 5-micron C18 125A 50x4.60 mm column and a linear gradient from 55% methanol: 1% acetonitrile in water to 100% methanol for 3 minutes. 100% methanol is held for 2 minutes. As an alternative, LC-MS spectra are obtained either using Agbei! 120086 VEES equipped with 6130 mass spectrometer operating during electrospray ionization (ES); Chromatographic data obtained using column 81ιίιη; · ι6ζι.ι 8W-Rask ΧΚ-ΟΌ8, 3.0x30

- 26 016912 mm, particle size 2.2 μm and a water-methanol gradient of 15 to 95% methanol for 2.2 min at a flow rate of 1.5 ml / min; retention at 95% methanol is used at the end of the gradient for 0.8 min; both mobile phases, both water and methanol, contain 0.1% formic acid.

Basic synthetic procedures

Compounds of formula (I) can be prepared using or using known methods (i.e., methods still used or described in the chemical literature)

For example, compounds of formula (I) can be prepared by a process in which compound (II) is reacted with compound (III), wherein K ₃ , K ₄ , K ₅ , K ₆ , K ₇ , P, O, V, ^, X , Υ, ζ and a are the groups defined above for compounds of formula (I), and T is a leaving group, for example, a halogen atom, methanesulfonyl, trifluoromethanesulfonyl, toluenesulfonyl, and the like.

_ζ _ νν ^<ν γ: - ^α > Η / (111} / ^{ζ Κ} '' к, N- (0) 3 — Κν -! - ι I ν— ₍ с) а — 4 — ν 'kg ^ρ κ ₄ аз base ||| θ (II) (I)

Base - base

The reaction is usually carried out in a solvent in the presence of a base.

The bases used in this reaction include, but are not limited to, inorganic bases, for example sodium carbonate, potassium carbonate, etc., organic bases, for example dimethylaminopyridine, triethylamine, diisopropylethylamine, 1,8-diazabicyclo- [5.4. 0] -7-undecene, etc.

Solvents that are used in this reaction include, but are not limited to, ethers, for example diethyl ether, tetrahydrofuran and the like, halogenated hydrocarbons, for example methylene chloride, chloroform, 1,2-dichloroethane and the like.

The reaction temperature is usually in the range of −78 to −150 ° C., preferably in the range of −20 to −80 ° C., and the reaction time is usually in the range of 1-72 hours.

After completion of the reaction, the compounds of formula (I) can be isolated using conventional methods, for example, adding water to the reaction mixture, extraction with an organic solvent, concentrating the extract, and the like. The isolated compound of formula (I) can be purified by methods such as chromatography, recrystallization and the like, if necessary.

Compounds of formula Ca) can be prepared using or using known methods for the formation of amides (i.e., methods used so far or described in the chemical literature)

Many procedures are available for the formation of an amide bond between amino derivatives, for example derivatives of α-aminonitrile of formula (II) and a carboxylic acid using condensing agents. Procedures have been developed using reagents such as carbodiimides as condensing agents for the formation of amides. Such carbodiimides include, for example, dicyclohexylcarbodiimide (OSS), diisopropylcarbodiimide (O [C), 1- (3-dimethylaminopropyl) -3 ethylcarbodiimide hydrochloride (BOC) and the like. Catalysts are also used, for example 1hydroxybenzotriazole (HOBT) and its derivatives. A summary of such methods can be found in Sotrgeepmma Otdashs Ttapk Gogtayopk, K.S. Lagosk, νί, и Rybikyetk (1989) p. 972-972. A general idea of such transformations is also available from Matsy'k Lbuapseb Otdashs Syetschyu: Keasyopk, Mesyashktk, apb 8 (gps1ige (8ίχ (1ι Ебююп), Мюйе1 В. .

Another common reaction for the preparation of amides is the interaction of acid halides with amines. Such a conversion is well known to those skilled in the art, and a review of such reactions is available from Matsy'k Lbuapseb Otdashs SjetShgu: Keasyopk, Mesyashktk, apb 8 (gps1ige (8ίχ (1ι Ebüyup), M1syaye1 V. 8thy apb 1epuyesyu, Rijkyega, (2007), p. 1427-1429.

Derivatives of α-aminonitrile of the formula (II) can be obtained by reacting carbonyl compounds of the general formula (IV) with a suitable source of cyanide, for example sodium cyanide, potassium cyanide, trimethylsilyl cyanide and the like, with amines of the general formula Β <5-ΝΗ ₂ , e.g. ammonia, methylamine, etc. and usually in the presence of an ammonium salt, for example, ammonium chloride and the like. This reaction is known to those skilled in the art as the synthesis of Strecker (see, for example, p. 1391 at Matsy'8 Lbuapseb Otdashs Syetshyu: Keasbopk, Mesyapshtk, ap 81gis1ige (§1x111 Ebyup), M1syaye1 V. 1peysyeb Riykjega (2007).

- 27 016912 'At VI

I * ₆ -νη ₂

Swagps1ez

Swashdes - cyanides

Carbonyl compounds of formula (IV) can be prepared by reacting ΝΗ-aryloazole of general formula (V) with a compound of general formula (VI) in which K ,, K ₂ , K ₃ , K ₄ , K ₅ , K ₇ , P, O .V, ED, X, Υ, a, t, and η are the groups defined above for compounds of formula (I), and T is a leaving group, for example, a halogen atom, methanesulfonyl, trifluoromethanesulfonyl, toluenesulfonyl, and the like.

(V) _(ΐν)

Base - base

The reaction is usually carried out in a solvent in the presence of a base.

The bases that are used in this reaction include, for example, but not limited to, inorganic bases, for example sodium carbonate, potassium carbonate and the like, organic bases, for example dimethylaminopyridine, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4 .0] -7-undecene, etc.

Solvents that are used in this reaction include, for example, but not limited to, acetone, ethers, for example diethyl ether, tetrahydrofuran, and the like, halogenated hydrocarbons, for example methylene chloride, chloroform, 1,2-dichloroethane, etc. P.

The reaction temperature is usually in the range of −78 to −150 ° C., preferably in the range of −20 to −80 ° C., and the reaction time is usually in the range of 1-72 hours.

After completion of the reaction, compounds of formula (IV) can be isolated using conventional methods, for example, adding water to the reaction mixture, extracting with an organic solvent, concentrating the extract, and the like.

The isolated compound of formula (IV) can be purified by methods such as chromatography, recrystallization and the like, if necessary.

2H-NΗ-aryloazole of the formula ^ a), (formula (V) with Ρ = Ν) are usually represented as their tautomeric structure of 1H-Ж-aryloazole (\ b). In particular, 2H-benzotriazole of the formula (Yy) and 2H-indazole of the formula (Yy) are usually represented as their alternative tautomeric forms, respectively, of 1H-benzotriazole of the formulas (4) or (Che) and 1H-indazole of the formula (Ϋβ).

A discussion of the tautomerism of heterocycles can be found in Thieu ThaiUtegb о o Не He1egosus1e§, A4uapse§ ίη He1egosusys SjetShgu 8irr1etep! 1, e4§. 1o5c E1giego, C1a4e Magap, A1ap K. Ka1n1khku ap4 Rao1bh4a, Asa4et1s Prge§8 RiByegk (1976).

In the preparation of carbonyl compounds of formula (Al) by reacting 1Η-NΗ-aryloazole of general formula (a) with a compound of general formula (VI), regioisomeric carbonyl compounds of formula OS are also obtained. They can be separated from the desired carbonyl compounds of formula (A) by a standard purification method known to those skilled in the art, but are not limited to liquid chromatography using conventional phase or reverse phase chromatography on silica gel columns or crystallization.

¹ N 'N C B T- [c _{) a} ^ 'K ° ° (VI) 'Ν K ₄ O ⁺ 4 1 w, 0 / a) (1Ua) ^k d \ (1Yb) o ^; to ₆

Ba $ e - foundation

Those derivatives of 'H-IN-aryloazole of general formula ^ a) that are not commercially available can be obtained using or using known methods (i.e., methods used so far or described in the chemical literature).

For example, a general method for producing 1H-benzotriazole of formula (4) or (^ e), where K ₁ , K ₂ , V, ED, X, Υ, Ζ, t and η are the groups defined above for compounds of formula (I) , can be found in Ogdashs 8up1ye515, Co11. wo1. 3, p. 106 (1955) in 1oigpa1 o £ He1gosusys SyetByu, yo1. 22, (1985), p.

- 28 016912

1165-1167. Halogenation of 1H-benzotriazole of the formula (Ub) or (Ue) can be carried out using procedures described in the literature, for example, those described by V. N. \ UPeu apb K.R. Nikkipd in 1sppa1 o £ (atepsap Syet1ca1 8ooe1u , (1957), rakek 4395-4400, and K. Korapkka e (a1. In Vyuoguds & Meb1S1pa1 Syetiu, uo1ite 13 (2005), district 3601 and in Vuuugudes & Meb1sta 1 Siuetuu, uoiti 12 (2004), p. 2617-2624.

Overall process for preparing 1H-indazole of formula (Vg), where _{s 2} In, V, ^, X, Υ , m and n groups are as defined above for compounds of formula (I), are described in the literature VA Vaiksi and 11 \ Uoo Υaηd in 1 па 1 1 о Не Не ос ос ((ос (ус К с й ет ет,,,,, о 21 21 21,,,,, 21 21 о недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно недавно p. 1153-1156 yo. 17 (2007), p. 3177-3180.

In one embodiment of the present invention, carbonyl compounds of formula (Sha), where O is alkoxymethylene (O = C-OB ₁₃ ) or methylene (P = CH), are formed by the oxidation of alcohol compounds of formula (UPa)

(UPA>

.V-

(1Ua)

OhShaNop - oxidation

Such transformations are well known to specialists in this field of technology, a brief description of such methods can be found in SotrgeyepkVe Ogdashs TgapkGogtayopk, USN Rijkjegk, (1989), V.S. Lagosk, r. 604-614. For example, they can be implemented using dimethyl sulfoxide reagents, for example, by reacting oxalyl chloride with dimethyl sulfoxide at a low temperature, it is known to those skilled in the art as Swern oxidation. They can also be realized using a nitroxyl radical, 2,2,6,6-tetramethylpiperidin-1-oxyl free radical (TEMPO), and similar reagents, and using hypervalent iodine reagents, i.e. the so-called Dess-Martin periodinan reagent (see, for example, pp. 1715-1728, Oh1bayop og Beyubgodepayop o £ A1сойо1к (о А1бейюбекбб КУЮпек in Magс'к Абгапсеб Огдашс Сететюу: Веасбопк, Ebup), M1syaye1 B. 8th apb 1epu Magsy, PeuPshegkaepse Riykyyegk (2007). Solvents used in the reaction include, but are not limited to, ethers such as diethyl ether, tetrahydrofuran and the like, halogenated hydrocarbons, for example methylene chloride, chloroform, 1,2-dichloroethane, etc. The reaction temperature is usually in the range of about -78 to -150 ° C, preferably in the range of -78 to -50 ° C, and the reaction time is usually in the range of 1-72 hours.

In another embodiment of the present invention, free alcohol derivatives of the formula (UPa) in which O is alkoxymethylene (O = C-OB ₁₃ ) or methylene (O = CH) are formed when the protecting group is cleaved from the corresponding protected alcohol derivative of the formula (Usa) where B1 ₂ represents a protected hydroxyl group. Protected hydroxyl groups used in the reaction include, but are not limited to, for example, ethers, for example p-methoxybenzyl ether and silyl ether, for example tert-butyldimethylsilyl ether (see, for example, Procodiophenyl ether (ye yubgohu1 dgoir p. 16-299 ίπ PrgoYusyge Sgoirk ίπ Ogdashs 8up (yek1k (Eoiby Ebyyup), ebk. Re (ex S.M. \ Wu (to apb Tieoboga ^. Sgeepe, ^ yeu-Shegkaepse Riyyekyegk (2007)).

Nuigokhu ог Proofer Sgoir C1eauade (No.) (UPa)

YooPghu! RgoSesyid Sgoir S1eauauge - Deprotection of the hydroxy group

In another embodiment of the present invention, compounds of formula (VISH) are formed by reacting compounds of formula (Sha) with an alcohol of formula B ₁₃ —OH and a base such as, but not limited to, potassium hydroxide, sodium hydroxide, and the like.

(1Xa)

(WUCH)

Non-Segosus ShaNop - Heterocyclization; Vase - foundation

The synthesis of 3-alkoxy-2-substituted 2H-indazoles is described in the chemical literature, for example, in OIGPA Ogdashs Sjet ^ uy, 2006, 71, 2687-2689 (Zb-Vopb-Yepods Ne1GosusUa (UP: 8U1U1SOK £ 3- A1kokhu2H-th ^ -io1ek LB AB M111k, M.2. Naaze ^, M.1. Nabbabt apb M.1. Kiby) apb 1n 1oita1 o £ Sotta (opa Sietkyu, 2007, 9, 171-177 ( 8up (ek1k o £ a Lbagu o £ 2-A1ku1-3-a1ku1oxu-2H- ^ πbaζo1e-6-sa ^ Loxat ^ beck bb A.B.Mb1k, R. Ma1opeu, E. Nakkapet, M. 1. Nabbab apb M. 1. Kiby.) However, none of the previous publications describes the synthesis of compounds of the formula (VISH).

In another embodiment of the present invention, compounds of formula (CSh) are formed upon heterocyclization of compounds of formula (1Xa) by reaction with a reducing agent, for example zinc.

R! to 5 γ m- | _{C) a} — _Gk , _ΝΟ 4 k, ( ^{| Xa} ) (CSh)

Not (erosus1Ea (1op - Heterocyclization; Ζίη <· - zinc

The synthesis of 2-substituted 2H-indazoles from derivatives of 2-nitrobenzylamines is described in the chemical literature, for example, 8in1, 2007, 16, 2509-2512 (A Νο \ ό1 apy EGPaegI 8n111em5 οί 2-Agu1-2NYi uo1e5 U1a 8nSa ₂ -Me her SUSGOaPop ίί 2-N ^ ΐ ^ οЬЬηηηуат ^ ^ ^ηη8 8Ь Отде Отд Отд Отд Отд Отд 8 8 8 8 ((((((Не1.), in 1 паигпа1 Не Не Не Не Не Не (Not C11еиисаиса11 8 8осос Неее Рег Рег Рег, Reg.Tgapkasyopk 1, 1973, 3, 319-324 (Rou№o81. Rgeragayop ίί 38iЬ8 (yi (her 2-A ^ y1-2Η-ρу ^ аζο1ο [4,3-b] ρуπй ^ е8. Лс1й-sa1a1u5ey Sus118a (1op οί 2-Agu 1at1po-te1yu 1-3puрупyруп Royeg apy I. Nigy) and in Teilabe, 1998, 54, 3197-3206 (2-8bb51b11bbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbbp -Pe apy C. Moses!). However, none of the above publications does not describe the synthesis of compounds of formula (νΠΒ).

In another embodiment of the present invention, compounds of formula (νίΠφ are formed by the interaction of aldehydes of formula (Xa) with compounds of formula (XI) in the presence of a reducing agent, for example, but not limited to, sodium cyanoborohydride, sodium borohydride, sodium triacetoxyborohydride, L-selectride® (tri- lithium sec-butyl (hydrido) borate), decaborane, etc.

K ₃

H ₂ H- | c) a - | - K, ₄ ok ₁₂ (XI)

Hegosus1 | hyop

Ζιηο

O'H _ν ο ₂ (Ha)

Keisyud adep (

(νΐΙΙφ

Ketzisch§ a ^ epT - Restorer

Solvents that are used in this reaction include, for example, but not limited to, ethers, for example diethyl ether, tetrahydrofuran and the like, halogenated hydrocarbons, for example methylene chloride, chloroform, 1,2-dichloroethane and the like. The reaction temperature is usually in the range of −78 to −150 ° C., preferably in the range of 0 to −80 ° C., and the reaction time is usually in the range of 1-72 hours.

Compounds of formula (Sha) can be prepared by reacting aldehydes of formula (X) with compounds of formula (XI) and reducing agents, for example, but not limited to, sodium cyanoborohydride, sodium borohydride, sodium triacetoxyborohydride, L-selectride® (tri-sec-butyl ( hydrido) lithium borate), decaborane, etc.

Such transformations are well known to specialists in this field of technology and are known as reductive amination; a brief description of such methods can be found in SoterNepmui Ogdas TgapzGogtaiopk, ΟΗΟΗ и и Ь Ь Ь к к (1989), I.S. Lagosk, r. 421-425. Solvents that are used in this reaction include, for example, but not limited to, ethers, for example diethyl ether, tetrahydrofuran and the like, halogenated hydrocarbons, for example methylene chloride, chloroform, 1,2-dichloroethane and the like. The reaction temperature is usually in the range of −78 to −150 ° C., preferably in the range of 0 to −80 ° C., and the reaction time is usually in the range of 1-72 hours.

Alternatively, compounds of formula (1Xa) can be prepared by reacting compounds of formula (XI) with compounds of formula (XII), where T represents a leaving group, for example, a halogen atom, methanesulfonyl, trifluoromethanesulfonyl, toluenesulfonyl, etc.

- 30 016912

When aldehydes of Formula (1Ha) are not commercially available, they can be prepared by oxidative cleavage of the alkene residue of the compounds of formula (XIII), wherein _{Κ! 4} and ₁₅ and are independently selected from _C1-C4 alkylcarbonyl and _C1-C4 alkyl.

Such transformations are well known to specialists in this field of technology and can be carried out, for example, with the participation of ozone, potassium permanganate and sodium metaperiodate. This method may optionally be carried out in a solvent, for example methylene chloride, diethyl ether, chloroform and usually at temperatures in the range of from about -100 to about 100 ° C. A summary of such methods can be found in Sotrtebepiu Ogdas TgapCottabopk, I.S. Lathosk, USN Pu118b8 (1989) p. 595, 596.

Derivatives of alkenes of the formula (XIII) in which Κ ₄₄ and K. _{15 are} independently selected from C ₄ -C ₄ alkylcarbonyl and C ₁ -C ₄ -alkyl can be obtained by condensation reactions of the compounds of formula (XIV), where K. ₁₆ represents an atom halogen or trifluoromethanesulfonyl and the like, with a compound of formula (XV), wherein M is trialkyltin, boric acid or boric acid ester and a palladium catalyst.

IA γ ^{Κ 16} (Xv) Μχ Ra11a <± it sa (a1ue1 ι B 1 ^to 15 V νο ₂ (Xiv) (Xx)

Ra11a <Nit sa! A1uM - Palladium catalyst

Such a conversion using a compound of formula (XV), where M is a trialkyltin, is known to those skilled in the art as Steele condensation. A description of such methods can be found in Matsb'k Abuapseb Ogdashs SNetMgu: Yaeasboik, Mesnapbth apb 8 (gis (ighe (δίχΐΗ Ебююп), М1сбе1 В. -795.

Solvents that are used in the reaction include, for example, but not limited to, ethers, for example tetahydrofuran, dioxane and the like, halogenated hydrocarbons, for example 1,2 dichloroethane and the like, aromatic solvents, for example benzene, toluene xylene and the like The reaction temperature is usually in the range of 0-200 ° C., preferably in the range of 20-120 ° C., and the reaction time is usually in the range of 1-72 hours.

Compounds of formula (Sha), wherein AND ₁₆ is a halogen atom, can be prepared from compounds of formula (XV) by forming a diazonium salt from the corresponding aniline and reacting with copper halides.

FAQ ₂ , ES1Y νν '' ^ν γ ^ΝΗ * og 1eg1-bu1u! Mx " og 150atu1p (χνΐ) Sorreg (Χΐνβ)

ΝβΝΟι, ac1 og GeGG-Li4u1sh4p1e og 180atu1sh (gye - ΝβΝΟϊ, acid or tert-butyl nitrile or isoaminonitrile

Sorreg ba1k1e - copper halide

Such transformations are known to specialists in this field of technology as the Sondmaer reaction (see, for example, Matsb'k Abuaiseb Ogdashs SNetMgu: Yaasboik, Mesnapb. p. 984-985).

Compounds of formula (Σι), where V is nitrogen or CI ₈ , K.yu is halogen and I ₂ and Itz either together or independently represent halogen or hydrogen, can be obtained by halogenation of the corresponding precursor of the compound of formula 0e) when using electrophilic halogenating agents known in the art, for example, but not limited to, Ν-iodosuccinimide, Ν-bromosuccinimide, Ν-chlorosuccinimide, 8е1ес (Piog® [1-chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2 ] octane bis- (tetrafluoroborate)] and the like.

- 31 016912

08) ^(s)

E1c1GORIpS ba1o epa1t§ agep (- Electrophilic halogenating agent

Compounds of formula (1e), where p is 1 or 2, can be prepared by oxidizing the corresponding precursor of a compound of formula (Ιί) using conventional oxidizing agents known in the art.

Specialists in the art should take into account that from the point of view of the methods described above, the order of the synthetic stages used can be changed and will depend, in particular, on factors such as the nature of other functional groups present in this substrate, the availability of key predecessors, and the strategy of protective groups should be adopted (if they exist) (see, for example, RgoKsyge Sgoirk ίη Ogdats 8up111e515 (Eöyb Ebüyi), ebk. ) Obviously, such factors will also influence the choice of reagents when used in these synthetic stages.

The compounds of examples 1-10 and 52-58 obtained according to the General reaction scheme

Final product:

ν = ^; A CK; X = _CK ; Υ = ^ Κ _Π ;

Ο = Ρ = Ν;

K3 = K4 = H; a = 1; K5 = methyl, butyl or CH2OH; K6 = H;

2 = C (O); K ₇ = p-phenyl-K.

Example 1. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.001).

4-Trifluoromethoxybenzoyl chloride (0.34 g) was added to a solution of 2-amino-3- (5-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (0.3 g) in dry DCM mixed with TEA (0.27 ml). The reaction mixture was stirred for 48 hours at room temperature. Silica gel was added to the reaction mixture and the solvent was evaporated under reduced pressure. The resulting crude product, placed on silica gel, was purified by chromatography (81O ₂ , heptane / EA) to give the title compound (the title compound) as a white powder (0.3 g, 54%). Κί = 0.7 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 424. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.74 (s, 3H), 5.39-5.49 (m, 2H), 7.48 (dd, 6 = 9.1, 1.9 Hz, 1H), 7.51 (br d, ί = 8.0 Hz, 2H), 7.93 (m, 2H), 8.01 (dd, ί = 9.1, 0.6 Hz, 1H) 8.13 (dd, ί = 1.9, 0.6 Hz, 1H) and 8.92 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -57.09 (s, 3E).

The starting material, 2-amino-3- (5-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile, was prepared as follows.

a. A mixture of 5-chloro-1H-benzotriazole (8 g), chloroacetone (6.5 ml), potassium carbonate (9.5 g) and potassium iodide (0.5 g) was stirred in acetone (90 ml) at room temperature for 48 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (5-chloro-2H-benzotriazol-2-yl) propan-2one as a clear oils [1.8 g, 16%, Κί = 0.6 (1: 1 EA / heptane)]. Two other regioisomers are also isolated, 1- (6-chloro-1H-benzotriazol-1-yl) propan-2-one [3.8 g, 35%, Κί = 0.45 (1: 1 EA / heptane)] and 1- (5-chloro-1Nbenzotriazol-1-yl) propan-2-one [3.2 g, 29%, Κί = 0.35 (1: 1 EA / heptane)].

Methanol (50 ml) was saturated with ammonia at -78 ° C for 5 minutes. The solution was allowed to warm to room temperature and then treated with sodium cyanide (0.7 g), ammonium chloride (0.9 g) and 1- (5-chloro-2H-benzotriazol-2-yl) propan-2-one (2.25 g ) The reaction mixture was stirred for 6 days at room temperature before concentration under reduced pressure. The residue is transferred to

- 32 016912 ethyl acetate, filtered and the filtrate was concentrated under reduced pressure to obtain a residue which was purified by chromatography (occupies 8 _2, heptane / EA) to give 2-amino-3- (5-chloro-2H-benzotriazole-2-yl) -2-methylpropionitrile in the form of a pale yellow solid (2.0 g, 79%). KG = 0.25 (1: 1 EA / heptane).

Example 2. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylbenzamide (compound No. 1.002).

Using a procedure similar to that described in Example 1, except for using 4 trifluoromethylbenzoyl chloride, the title compound was isolated as a white solid (0.12 g, 71%). KG = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 408, ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.40-5.52 (m, 2H ), 7.48 (dd, 1 = 9.1, 1.9 Hz, 1H), 7.88-7.93 (m, 2H), 7.99 (br d, 1 = 7.8 Hz, 1H ), 8.03 (d, 1 = 0.6 Hz, 1H), 8.13 (dd, 1 = 1.9, 0.6 Hz, 1H) and 9.04 (s, 1H).

Example 3. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.003).

Using a procedure similar to that described in Example 1, except for using 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid (1.4 g, 75%). KG = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 440. ¹ H NMR: (400 MHz, DMSO-b6): 1.74 (s, 3H), 5.39-5.50 (m, 2H), 7.48 (dd, 1 = 9.1, 1.9 Hz, 1H), 7.85-7.92 (m, 4H), 8.01 (dd, 1 = 9.1, 0.7 Hz, 1H), 8.13 (dd, 1 = 1.9, 0.6 Hz, 1H) and 9.01 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -41.93 (s, 3P).

Example 4. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-phenoxybenzamide (compound No. 1.032).

Using a procedure similar to that described in Example 1, except for using 4 phenoxybenzoyl chloride, the title compound was isolated as a white solid (57 mg, 65%). MS (ES): M / Ζ [M + H] = 432. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.74 (s, 3H), 5.40-5.46 (m, 2H), 7.04-7.16 (m, 4H), 7 , 20-7.27 (m, 1H), 7.42-7.51 (m, 3H), 7.82-7.88 (m, 2H), 7.99-8.05 (m, 1H) 8.12-8.15 (m, 1H,) and 8.74 (s, 1H).

4-Phenoxybenzoyl chloride is prepared by reacting 4-phenoxybenzoic acid with oxalyl chloride.

Example 5. No. [2- (2H-Benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.004).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid (0.1 g, 51%). KG = 0.55 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 390. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.39-5.49 (m, 2H), 7.45 (br s, 2H), 7.51 ( d, 1 = 8.0 Hz, 2H), 7.94 (br d, 1 = 7.5 Hz, 4H) and 8.93 (s, 1H).

2-amino-3- (2H-benzotriazol-2-yl) -2-methylpropionitrile [1.9 g, 97%, KG = 0.2 (1: 1 EA / heptane)] was obtained using a procedure similar to that described in Example 1, parts a and b, except that the starting material was 1 # -benzotriazole.

Example 6. No. [2- (2H-Benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.005).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (2H-benzotriazol-2-yl) -2-methylpropionitrile described in Example 5 and 4trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid (0, 12 g, 59%). KG = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 406. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.39-5.50 (m, 2H), 7.46 (dd, 1 = 6.6, 3.1 Hz, 2H), 7.85-7.95 (m, 6H) and 9.01 (s, 1H).

Example 7. No. [1-Cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.006).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-2-methyl-3- (5-methyl-2H-benzotriazol-2-yl) propionitrile, the title compound was isolated as a white solid (0.09 g, 45%). KG = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 404. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.73 (s, 3H), 2.45 (s, 3H), 5.34-5.43 (m, 2H), 7.30 (dd , 1 = 8.8, 1.4 Hz, 1H), 7.52 (d, 1 = 8.0 Hz, 2H), 7.68 (d, 1 = 1.0 Hz, 1H), 7.82 (d, 1 = 8.8 Hz, 1H), 7.90-7.97 (m, 2H) and 8.91 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-Y6): -57.08 (s, 3P).

2-amino-2-methyl-3- (5-methyl-2H-benzotriazol-2-yl) propionitrile [2.1 g, 92%, KG = 0.2 (1: 1

EA / heptane)] is obtained using a procedure similar to that described in Example 1, parts a and b, except that the starting material is 5-methyl-1H-benzotriazole.

Example 8. No. [1-Cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.007).

Using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (5-methyl-2H-benzotriazol-2-yl) propionitrile described in example 7 and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as white solid (0.12 g, 57%). KG = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 420. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.73 (s, 3H), 2.45 (s, 3H), 5.34-5.44 (m, 2H), 7.30 (dd, 1 = 8.8, 1.4 Hz, 1H), 7.68 (d, 1 = 1.0 Hz, 1H), 7.82 (d, 1 = 8.8 Hz,

- 33 016912

1H), 7.84-7.94 (m, 4H) and 8.91 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -41.94 (s, 3P).

Example 9. No. [2- (5-Chloro-6-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.040).

Using a procedure similar to that described in example 1, except for the use of 2 amino-3- (5-chloro-6-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (90 mg), the title compound was isolated as a white solid substances (125 mg, 79%). KG = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 438. ^! H NMR: (400 MHz, DMSO-b6): 1.73 (s, 3H), 2.46 (s, 3H), 5.38 (d, 1 = 13.4 Hz, 1H), 5.44 ( d, 1 = 13.3 Hz, 1H), 7.52 (d, 1 = 8.0 Hz, 2H), 7.93 (d, 1 = 8.8 Hz, 2H), 7.96 (s, 1H ), 8.13 (s, 1H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.08 (s, 3P).

2-amino-3- (5-chloro-6-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile [2.1 g, 92%, KG = 0.2 (1: 1 EA / heptane)] obtained using a procedure similar to that described in example 1, parts a and b, except that the starting material was 6-chloro-5-methyl-1H-benzotriazole.

Example 10. No. [2- (5-Chloro-6-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.041).

When using a procedure similar to that described in example 1, except for the use of 2 amino-3- (5-chloro-6-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (90 mg described in example 9) and 4- trifluoromethylthiobenzoyl chloride (0.1 ml), the title compound is isolated as a white solid (152 mg, 93%). 11'0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 454. ^! H NMR: (400 MHz, DMSOb6): 1.73 (s, 3H), 2.46 (s, 3H), 5.38 (d, 1 = 13.4 Hz, 1H), 5.45 (d, 1 = 13.4 Hz, 1H), 7.87 (d, 1 = 8.5 Hz, 2H), 7.91 (d, 1 = 8.6 Hz, 2H), 7.96 (s, 1H) 8.13 (s, 1H); and 9.00 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -41.93 (s, 3P).

The compounds of examples 11-51 receive according to the General reaction scheme:

Final product:

ν = ^ Β ₈ ; V CK; X = CK ₁₀ ; Υ = € -Β _π ;

Ο = Ρ = Ν;

K ₃ N; a = 1; K, = CH ₃ ; 1C11;

Ζ = ί. '(Ό); K ₇ = p-phenyl-K.

Example 11. No. [1-Cyano-1-methyl-2- (5-trifluoromethyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.008).

Using a procedure similar to that described in Example 1, except for the use of 2amino-2-methyl-3- (5-trifluoromethyl-2H-benzotriazol-2-yl) propionitrile, the title compound was isolated as a white solid (65 mg, 26% ) KG = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 458. ¹ H NMR: (400 MHz, DMSO-b6): 1.76 (s, 3H), 5.47-5.57 (m, 2H), 7.50 (d, 1 = 8.0 Hz, 2H) 7.71 (dd, 1 = 9.0, 1.6 Hz, 1H), 7.93 (m, 2H), 8.20 (d, 1 = 9.0 Hz, 1H), 8.50 ( broad s, 1H) and 8.91 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -61.17 (s, 3P) and -57.09 (s, 3P).

2-amino-2-methyl-3- (5-trifluoromethyl-2H-benzotriazol-2-yl) propionitrile [1.2 g, 69%, KG = 0.35 (1: 1 EA / heptane)] is obtained using procedures similar to that described in example 1, parts a and b, except that the starting material was 5-trifluoromethyl-1H-benzotriazole, which was prepared as follows.

A mixture of 2-nitro-4-trifluoromethylaniline (12 g) and activated palladium on activated carbon (0.6 g) in methanol was hydrogenated using one hydrogen atmosphere with stirring for 1 h. The reaction mixture was filtered through a pad of diatomaceous earth and the filtrate was concentrated at reduced pressure to form a residue. This residue was then dissolved in acetic acid (100 ml) and water (15 ml) and cooled to 0 ° C. before adding hydrochloric acid (4 ml) and a solution of sodium nitrite (4.4 g) in water (10 ml). The mixture was stirred at room temperature for 2 hours and diluted with water. The resulting solid was filtered off, washed with water and dried to give an off-white solid (8.0 g, 73%).

Example 12. No. [1-Cyano-1-methyl-2- (5-trifluoromethyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethyl

- 34 016912 thiobenzamide (compound No. 1.009).

Using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (5-trifluoromethyl-2H-benzotriazol-2-yl) propionitrile described in example 11 and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as white solid (0.16 g, 61%). W = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 474. Ή NMR: (400 MHz, chloroform-b): 1.88 (s, 3H), 5.39 (dd, 6 = 11.8, 13.7 Hz, 2H), 7.38 (br s, 1H) , 7.65 (d, 1 = 9.1 Hz, 1H), 7.75-7.88 (m, 4H), 8.02 (d, 1 = 9.0 Hz, 1H) and 8.25 ( broad s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -63.01 (s, 3P) and -42.23 (s, 3P).

Example 13. Ν- [1-Cyano-2- (5,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.010).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid (72 mg, 28 %). W = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 458. ¹ H NMR: (400 MHz, DMSO-b6): 1.74 (s, 3H), 5.41-5.51 (m, 2H), 7.51 (d, 1 = 8.1 Hz, 2H) 7.93 (d, 1 = 8.8 Hz, 2H), 8.43 (br s, 2H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.10 (s, 3P).

2-amino-3- (5,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile [0.35 g, 79%, Raman = 0.25 (1: 1 EA / heptane)] is obtained at using a procedure similar to that described in example 1, parts a and b, except that the starting material is 5,6-dichloro-1H-benzotriazole, which is prepared as follows.

4,5-Dichlorobenzene-1,2-diamine (4.8 g) was dissolved in acetic acid (45 ml) and water (15 ml) and cooled to 0 ° C before adding hydrochloric acid (2 ml) and a nitrite solution sodium (2.8 g) in water (15 ml). The mixture was stirred at room temperature for 30 minutes and diluted with water. The resulting solid is filtered off, washed with water and dried. The resulting crude product is dissolved in hot ethanol. Any remaining solid is filtered off and the filtrate allowed to cool. Adding water leads to the formation of a solid, which is filtered off, washed with water and dried, which leads to the formation of a brown solid (2.8 g, 55%).

Example 14. N- [1-Cyano-2- (5,6-dichloro-2Η-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.011).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile described in Example 13 and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as white solid (90 mg, 34%). MS (ES): M / Ζ [M + H] = 474. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.74 (s, 3H), 5.41-5.51 (m, 2H), 7.827.91 (m, 4H), 8.41 (br s , 2H) and 9.00 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -41.94 (s, 3P).

Example 15. Ν- [1-Cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.012).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (4,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid (83 mg, 33 %), Raman = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 458. ¹ H NMR: (400 MHz, DMSO-b6): 1.75 (s, 3H), 5.40-5.55 (m, 2H), 7.47 (d, 1 = 8.25 Hz, 2H) 7.69 (dd, 1 = 1.5, 0.8 Hz, 1H), 7.92 (d, 1 = 8.8 Hz, 2H), 8.13 (d, 1 = 1.6 Hz, 1H) and 8.87 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.19 (s, 3P).

2-amino-3- (4,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile [0.35 g, 63%, Raman = 0.35 (1: 1 EA / heptane)] is obtained at using a procedure similar to that described in example 1, parts a and b, except that the starting material is 5,7-dichloro-1H-benzotriazole. 5,7-Dichloro-1Nbenzotriazole (11 g, 99%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 2,4-dichloro-6-nitroaniline (12 g).

Example 16. N- [1-Cyano-2- (4,6-dichloro-2Η-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.013).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (4,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile described in Example 15 and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as white solid (50 mg, 20%). W = 0.7 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 475. NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.40-5.56 (m, 2H), 7.65 (m, 1H), 7.79-7.95 (m, 4H), 8.10 (m, 1H) and 8.95 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.05 (s, 3P).

Example 17. N- [1-Cyano-2- (4,6-dichloro-2Η-benzotriazol-2-yl) -1-methylethyl] biphenyl-4-carboxamide (compound No. 1.046).

Using a procedure similar to that described in example 1, except for the use of 2 amino-3- (4,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile described in example 15 and 4biphenylcarbonyl chloride, the title compound is isolated as white solid (32 mg). MS (ES): M / Ζ [M + H] = 450. NMR: (400 MHz, DMSO-b ₆ ): 1.78 (s, 3H), 5.45 (d, 1 = 13.3 Hz, 1H), 5.55 (d, 1 = 13.3 Hz, 1H), 7.43 (m, 1H), 7.51 (t, 1 = 7.5 Hz, 1H), 7.70-7.78 (m, 3H), 7.81 (d, 1 = 8 4 Hz, 2H), 7.90 (d, 1 = 8.5 Hz, 2H), 8.18 (d, 1 = 1.6 Hz, 1H) and 8.83 (s, 1H).

- 35 016912

Example 18. No. [1-Cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-tert-butylbenzamide (compound No. 1.053).

Using a procedure similar to that described in example 1, except for the use of 2 amino-3- (4,6-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile described in example 15 and 4-tert-butylbenzoyl chloride, the title compound was isolated as a white solid (80 mg). MS (ES): M / Ζ [M + H] = 430. NMR: (400 MHz, DMSO-6 ₆ ): 1.30 (s, 9H), 1.75 (s, 3H), 5.47 (q, 1 = 17.8 Hz, 2H), 5.51 ( d, 1 = 8.3 Hz, 2H), 7.70-7.76 (m, 3H), 8.18 (d, 1 = 1.5 Hz, 1H) and 8.70 (br s, 1H) .

Example 19. No. [2- (4-Chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.014).

Using a procedure similar to that described in Example 1, with the exception of using 2amino-3- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid (0, 66 g, 82%). HB = 0.7 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 492. Ί1 NMR: (400 MHz, DMSO-be): 1.11 (s, 3H), 5.46-5.67 (m, 2H), 7.50 (d, 1 = 8.1 Hz, 2H), 7.89-7.96 (m, 2H), 8.56 (br s, 1H), 8.87 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-6 ₆ ): -61.07 (s, 3P) and -57.15 (s, 3P).

2-amino-3- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile [1.7 g, 89%,

GH = 0.35 (1: 1 EA / heptane)] is obtained using a procedure similar to that described in Example 1, parts a and b, except that the starting material is 7-chloro-5-trifluoromethyl-1H-benzotriazole. 7-Chloro-5-trifluoromethyl-1H-benzotriazole (4.6 g, 99%) was obtained using the procedure similar to that described in example 11, part a, except that the starting material was 4-amino-3-chloro- 5-nitrobenzotrifluoride (5 g).

Example 20. No. [2- (4-Chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.015).

Using a procedure similar to that described in Example 1, except for using 2amino-3- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile described in Example 19 and the 4-trifluoromethylthiobenzoyl chloride title compound isolated as a white solid (0.45 g, 90%). GV = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 508. ^! H NMR: (400 MHz, DMSO-66): 1.77 (s, 3H), 5.49-5.65 (m, 2H), 7.84-7.93 (m, 5H), 8.56 (d, 1 = 1.1 Hz, 1H) and 8.95 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-66): -61.09 (s, 3P) and -42.03 (s, 3P).

Example 21. No. [1-Cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.016).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-cyano-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid (0.25 g, 45 %). GV = 0.45 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 415. ¹ H NMR: (400 MHz, DMSO-66): 1.76 (s, 3H), 5.46-5.59 (m, 2H), 7.51 (d, 1 = 8.0 Hz, 2H) 7.76 (dd, 1 = 8.8, 1.4 Hz, 1H), 7.89-7.96 (m, 2H), 8.17 (dd, 1 = 8.9, 0.9 Hz) , 1H), 8.77 (m, 1H) and 8.93 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-66): -57.11 (s, 3P).

2-amino-3- (5-cyano-2H-benzotriazol-2-yl) -2-methylpropionitrile [0.85 g, 75%, HB = 0.15 (1: 1 EA / heptane)] is obtained using the procedure , similar to that described in example 1, parts a and b, except that the starting material was 5-cyano-1H-benzotriazole. 5-Cyano-1Nbenzotriazole (5.7 g, 65%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 4-amino-3-nitrobenzonitrile (10 g).

Example 22. No. [1-Cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.017).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-cyano-2H-benzotriazol-2-yl) -2-methylpropionitrile described in Example 21 and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid substances (0.46 g, 81%). GV = 0.45 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 431. Ή NMR: (400 MHz, DMSO-6 ₆ ): 1.76 (s, 3H), 5.46-5.59 (m, 2H), 7.76 (dd, 1 = 8.9, 1.3 Hz, 1H), 7.84-7.93 (m, 4H), 8.18 (d, 1 = 8.9 Hz, 1H), 8.78 (br s, 1H) and 9.01 (br s , 1H). ¹⁹ P NMR (376 MHz, DMSO-6 ₆ ): -41.93 (s, 3P).

Example 23. No. [2- (4,6-bis- (trifluoromethyl) -2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.018).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (4,6-bis- (trifluoromethyl) -2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound is isolated as a white solid ( 0.41 g, 88%). GV = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 526. Ή NMR: (400 MHz, DMSO-6 ₆ ): 1.79 (s, 3H), 5.61 (dd, 1 = 55.9, 13.3 Hz, 2H), 7.48 (d, 1 = 8.0 Hz, 2H), 7.88-7.91 (m, 2H), 8.13 (s, 1H), 8.83 (s, 1H) and 8.98 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-6 ₆ ): -57.18 (s, 3P), -61.00 (s, 3P) and -61.59 (s, 3P).

2-amino-3- (4,6-bis- (trifluoromethyl) -2H-benzotriazol-2-yl) -2-methylpropionitrile [1.5 g, 77%,

GH = 0.3 (1: 1 EA / heptane)] is obtained using a procedure similar to that described in example 1, part a and b, except that the starting material is 5,7-bis- (trifluoromethyl) -2H- benzotriazole. 5,7-bis- (trifluoromethyl) -2H-benzotriazole (5.2 g, 99%) was obtained using the procedure similar to that described in example 13, part a, except that the starting material was 3,5-bis

- 36 016912 (trifluoromethyl) -1,2-phenylenediamine (5 g).

Example 24. No. [2- (4,6-bis- (trifluoromethyl) -2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethylthiobenzamide (compound No. 1.019).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (4,6-bis- (trifluoromethyl) -2H-benzotriazol-2-yl) -2-methylpropionitrile described in example 23 and 4-trifluoromethylthiobenzoyl chloride the title compound was isolated as a white solid (0.40 g, 83%). HB = 0.7 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 542. ¹ H NMR: (400 MHz, DMSO-b6): 1.79 (s, 3H), 5.62 (dd, 1 = 60.6, 13.3 Hz, 2H), 7.76-7.97 ( m, 4H), 8.13 (s, 1H), 8.92 (s, 1H) and 8.97 (s, 1H). ¹⁹ G NMR (376 MHz, DMSO-b6): -61.62 (s, 3B), -61.04 (s, 3B) and -42.10 (s, 3B).

Example 25. No. [2- (5-Bromo-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.020).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-bromo-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid (0.36 g, 72 %). GV = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 468. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.74 (s, 3H), 5.44 (dd, 1 = 26.8, 13.3 Hz, 2H), 7.51 (d, 1 = 8.0 Hz, 2H), 7.58 (dd, 1 = 9.1, 1.8 Hz, 1H), 7.91-7.96 (m, 2H), 7.96 (dd, 1 = 9.1, 0.5 Hz, 1H), 8.29 (dd, 1 = 1.7, 0.5 Hz, 1H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.09 (s, 3B).

2-amino-3- (5-bromo-2H-benzotriazol-2-yl) -2-methylpropionitrile [1.7 g, 93%, HB = 0.35 (1: 1

EA / heptane)] is obtained using a procedure similar to that described in Example 1, parts a and b, except that the starting material is 5-bromo-1H-benzotriazole. 5-Bromo-1H-benzotriazole is obtained using a procedure similar to that described in example 13, part a, except that the starting material is 4-bromo-1,2-diaminobenzene.

Example 26. No. [2- (5-Bromo-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylbenzamide (compound No. 1.021).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-bromo-2H-benzotriazol-2-yl) -2-methylpropionitrile described in Example 25 and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid substances, the title compound is isolated as a white solid (0.45 g, 87%). GV = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 484. ^! H NMR: (400 MHz, DMSO-be): 1.74 (s, 3H), 5.36-5.53 (m, 2H), 7.58 (dd, 1 = 9.1, 1.8 Hz) , 1H), 7.84-7.92 (m, 4H), 7.95 (dd, 1 = 9.1, 0.5 Hz, 1H), 8.29 (dd, 1 = 1.7, 0 6 Hz, 1H) and 9.00 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -41.93 (s, 3B).

Example 27. No. [2- (6-Chloro-4-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.033).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-4-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid (192 mg , 55%). mS (ES): M / Ζ [M + H] = 438. ¹ H NMR: (400 MHz, DMSO-b6): 1.74 (s, 3H), 2.47 (s, 3H), 5.35-5.51 (m, 2H), 7.27 (s, 1H), 7.52 (d, 1 = 8.0 Hz, 2H), 7.88-7.95 (m, 3H) and 8.84 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.12 (s, 3B).

2-amino-3- (6-chloro-4-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (0.4 g, 67%) was obtained using a procedure similar to that described in example 1, part a and B, except that the starting material is 5-chloro-7-methyl-1H-benzotriazole. 5-Chloro-7-methyl-1H-benzotriazole (4.35 g, 97%) was obtained using the procedure similar to that described in example 11, part a, except that the starting material was 4-chloro-2-methyl- 6-nitroaniline (5 g).

Example 28. Ν- [2 - (6-Chloro-4-methyl-2H-benzotriazole-2-yl) - 1-cyano -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.034).

Using a procedure similar to that described in example 1, except for the use of 2 amino-3- (6-chloro-4-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile described in example 27 and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid (233 mg, 64%). MS (ES): M / Ζ [M + H] = 454. NMR: (400 MHz, DMSO-b ₆ ): 1.74 (s, 3H), 2.47 (s, 3H), 5.44 (dd, 1 = 57.5, 13.3 Hz, 2H), 7.27 (s, 1H), 7.79-7.99 (m, 5H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.01 (s, 3B).

Example 29. No. [2- (6-Chloro-4-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-phenoxybenzamide (compound No. 1.039).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-4-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (60 mg described in Example 27) and 4- phenoxybenzoyl chloride (0.067 ml), the title compound is isolated as a white solid (90 mg, 84%). MS (ES): M / Ζ [M + H] = 446. NMR: (400 MHz, DMSO-b ₆ ): 1.73 (s, 3H), 2.47 (s, 3H),

5.38 (d, 1 = 13.3 Hz, 1H), 5.45 (d, 1 = 13.3 Hz, 1H), 7.08 (t, 1 = 8.25 Hz, 4H), 7, 23 (t, 1H), 7.28 (s, 1H), 7.45 (t, 2 N), 7.84 (d, 1 = 8.79 Hz, 2 N), 7.91 (m, 1H ) and 8.68 (s, 1H).

4-Phenoxybenzoyl chloride is prepared by reacting 4-phenoxybenzoic acid with oxalyl chloride.

- 37 016912

Example 30. No. [1-Cyano-1-methyl-2- (5-trifluoromethoxy-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.035).

Using a procedure similar to that described in Example 1, with the exception of using 2 amino-3- (5-trifluoromethoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg), the title compound was isolated as a white solid (140 mg , 85%). MS (ES): M / Ζ [M + H] = 474. ¹ H NMR: (400 MHz, DMSO-b6): 1.75 (s, 3H), 5.44 (d, 1 = 13.3 Hz, 1H), 5.51 (d, 1 = 13.4 Hz , 1H), 7.45-7.52 (m, 3H), 7.93 (d, 1 = 8.8 Hz, 2H), 8.06 (br s, 1H), 8.12 (d, 1H , 1 = 9.9 Hz) and 8.89 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b6): -57.42 (s, 3E) and -57.11 (s, 3E).

2-amino-3- (5-trifluoromethoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile (0.24 g) was obtained using the procedure similar to that described in example 1, part a and b, except that the starting material is 5-trifluoromethoxy-1H-benzotriazole (3.2 g). 5-Trifluoromethoxy-1H-benzotriazole (3.4 g, 74%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 2-nitro-4-trifluoromethoxyaniline (5 g).

Example 31. No. [1-Cyano-1-methyl-2- (5-trifluoromethoxy-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.036).

When using a procedure similar to that described in example 1, except for the use of 2 amino-3- (5-trifluoromethoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg described in example 30) and 4-trifluoromethylthiobenzoyl chloride (0, 12 ml), the title compound is isolated as a white solid (142 mg, 83%). MS (ES): M / Ζ [M + H] = 490. ¹ H NMR: (400 MHz, chloroform-b): 1.75 (s, 3H), 5.48 (d, 1 = 13.4 Hz, 1H), 5.52 (d, 1 = 13.3 Hz, 1H), 7.47 (d, 1 = 10.6 Hz, 1H), 7.85-7.91 (m, 4H), 8.05 (br s, 1H), 8.12 (d, 1H, 1 = 9.3 Hz) and 8.98 (br s, 1H). ¹⁹ E NMR (376 MHz, chloroform-b): -57.43 (s, 3E) and -41.96 (s, 3E).

Example 32. No. [2- (6-Chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.037).

Using a procedure similar to that described in Example 1, with the exception of using 2amino-3- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg), the title compound was isolated as a white solid substances (148 mg, 91%). MS (ES): M / Ζ [M + H] = 492. ¹ H NMR: (400 MHz, DMSO-b6): 1.77 (s, 3H), 2.47 (s, 3H), 5.46 (d, 1 = 13.2 Hz, 1H), 5.60 (d, 1 = 13.4 Hz, 1H), 7.49 (d, 1 = 8.0 Hz, 2H), 7.89 (d, 1 = 8.8 Hz, 2H), 7.96 (s , 1H), 8.56 (s, 1H) and 8.85 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b6): -61.51 (s, 3E) and -57.16 (s, 3E).

2-amino-3- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (0.82 g) was obtained using a procedure similar to that described in example 1, part a and b, for except that the starting material is 5-chloro-7-trifluoromethyl-1H-benzotriazole (2.5 g). 5-Chloro-7-trifluoromethoxy-1H-benzotriazole (2.5 g, 55%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 2-amino-5-chloro-3-nitrobenzotrifluoride ( 5 g).

Example 33. Ν- [2 - (6-Chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) - 1-cyano -1-methylethyl] -4 trifluoromethylthiobenzamide (compound No. 1.038).

When using a procedure similar to that described in example 1, except for the use of 2amino-3- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg described in example 32) and 4- trifluoromethylthiobenzoyl chloride (0.12 ml), the title compound is isolated as a white solid (142 mg, 85%). MS (ES): M / Ζ [M + H] = 508. NMR: (400 MHz, DMSO-b ₆ ): 1.77 (s, 3H), 2.47 (s, 3H), 5.46 (d, 1 = 13.3 Hz, 1H), 5.62 ( d, 1 = 13.3 Hz, 1H), 7.82-7.88 (m, 4H), 7.96 (s, 1H), 8.57 (s, 1H) and 8.93 (s, 1H) ) ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -42.05 (s, 3E) and -61.51 (s, 3E).

Example 34. Ν- [2 - (6-Chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) - 1-cyano -1-methylethyl] -4 phenoxyobenzamide (compound No. 1.042).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg described in Example 32) and 4- phenoxybenzoyl chloride (0.10 ml), the title compound is isolated as a white solid (95 mg, 58%). Κί = 0.75 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 500. NMR: (400 MHz, DMSObe): 1.76 (s, 3H), 2.47 (s, 3H), 5.47 (d, 1 = 13.3 Hz, 1H), 5.57 (d, 1 = 13.3 Hz, 1H), 7.04-7.12 (m, 4H), 7.22 (t, 1 = 7.4 Hz, 1H), 7.97 (s, 1H), 8.57 (s, 1H) and 8.69 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -61.41 (s, 3E).

4-Phenoxybenzoyl chloride is prepared by reacting 4-phenoxybenzoic acid with oxalyl chloride.

Example 35. No. [2- (4-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.043).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (4-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg), the title compound was isolated as a white solid (142 mg , 80%). Κί = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 424. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.77 (s, 3H), 5.43 (d, 1 = 13.4 Hz, 1H), 5.54 (d, 1 = 13.4 Hz , 1H), 7.46 (t, 1H), 7.50 (d, 1 = 7.9 Hz, 2H), 7.59 (d, 1 = 6.8 Hz, 1H), 7.91-7.97 (m, 3H) and 8.90 (s, 1H). ¹⁹ E NMR (376 MHz, DMSObb): -57.12 (s, 3E).

- 38 016912

2-amino-3- (4-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (0.3 g) was obtained using the procedure similar to that described in example 1, parts a and b, except that starting material is 7-chloro-1H-benzotriazole (1.0 g). 7-Chloro-1H-benzotriazole (1.0 g, 23%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 3-chloro-2-nitroaniline (5 g).

Example 36. No. [2- (4-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.044).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (4-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg described in example 35) and 4 trifluoromethylthiobenzoyl chloride (0.1 ml ), the title compound is isolated as a white solid (130 mg, 70%). W = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 440. NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.43 (d, 1 = 13.3 Hz, 1H), 5.55 (d, 1 = 13.4 Hz, 1H), 7.46 (t, 1 = 8.0 Hz, 1H), 7.59 (d, 1 = 6.7 Hz, 1H), 7.75-7.95 (m, 5H) and 8, 97 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -41.98 (s, 3E).

Example 37. No. [2- (4-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-phenoxybenzamide (compound No. 1.045).

When using a procedure similar to that described in example 1, except for the use of 2amino-3- (4-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (100 mg described in example 35) and 4phenoxybenzoyl chloride (0.10 ml ), the title compound is isolated as a white solid (70 mg, 38%). W = 0.7 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 432. NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.43 (d, 1 = 13.3 Hz, 1H), 5.50 (d, 1 = 13.3 Hz, 1H), 7.04-7.10 (m, 4H), 7.22 (t, 1 = 7.4 Hz, 1H), 7.43-7.48 (m, 3H), 7.59 (d , 1 = 6.6 Hz, 1H), 7.84 (d, 1 = 8.9 Hz, 2H), 7.94 (d, 1 = 8.0 Hz, 1H) and 8.73 (s 1H) .

4-Phenoxybenzoyl chloride is prepared by reacting 4-phenoxybenzoic acid with oxalyl chloride.

Example 38. No. [2- (4-Bromo-6-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.060).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (4-bromo-6-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (1.0 g), the title compound was isolated as white solid (1.5 g, 90%). Κί = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 502. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.42 (d, 1H), 5.53 (d, 1H), 7.51 (d, 1 = 8, 0 Hz, 2H), 7.86 (d, 1 = 1.6 Hz, 1H), 7.92 (d, 1 = 8.8 Hz, 2H), 8.20 (d, 1 = 1.6 Hz , 1H) and 8.88 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-J6): -57.1 (s, 3E).

2-amino-3- (4-bromo-6-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile was obtained using the procedure similar to that described in example 1, parts a and b, except that the starting material is 7-bromo-5-chloro-1H-benzotriazole. 7-Chloro-5-chloro-1H-benzotriazole (7.6 g, 99%) was obtained using a procedure similar to that described in example 13, part a, except that the starting material was 3-bromo-5-chloro- 2-diaminobenzene, which is prepared as follows.

a. A mixture of 4-chloro-2-nitroaniline (10 g) and Ν-bromosuccinimide (11.3 g) in acetonitrile (200 ml) was heated at 70 ° C. overnight. The mixture was concentrated under reduced pressure, then poured into water and allowed to stir at room temperature for 1 hour. The resulting solid was filtered off, washed with water and dried. The resulting crude product, placed on silica gel, was purified by chromatography (81O ₂ , heptane / EA) to give 2-bromo-4-chloro-6-nitroaniline as a yellow solid (11.5 g, 79%). KG = 0.6 (3: 7 EA / heptane).

b. To an intensively stirred suspension of iron powder (1.1 g) in ethanol (10 ml) was added concentrated hydrochloric acid (2.5 ml) and the mixture was heated at 65 ° C. After 4 hours, a 25% aqueous solution of ammonium chloride (4 ml) was added, after which a solution of 2-bromo-4-chloro-6-nitroaniline (1 g) in ethanol was slowly added. After 3 hours, the mixture was allowed to cool to room temperature, and a CeSe® filter agent was added directly to the mixture. The suspension is filtered through a layer of a CeChe® filter agent. The filtrate was concentrated under reduced pressure, dissolved in ethyl acetate and filtered through a layer of a CeSe® filter agent. The filtered solution was treated with saturated sodium bicarbonate, washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain 3-bromo-5-chloro-2-diaminobenzene as a grayish-white solid (0.86 g, 98%). Κί = 0.25 (3: 7 EA / heptane).

Example 39. No. [1-Cyano-1-methyl-2- (4,5,7-trichloro-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.064).

Using a procedure similar to that described in Example 1, except for the use of 2amino-2-methyl-3- (4,5,7-trichloro-2H-benzotriazol-2-yl) propionitrile (150 mg), the title compound was isolated as white solid (210 mg, 87%). Κί = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 492. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.76 (s, 3H), 5.45 (d, 1H), 5.59 (d, 1H), 7.47 (d, 1 = 8, 25 Hz, 2H), 7.69 (dd, 1 = 1.5, 0.8 Hz, 1H), 7.81-8.04 (m, 3H) and 8.83 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -57.1 (s, 3E).

2-amino-2-methyl-3- (4,5,7-trichloro-2H-benzotriazol-2-yl) propionitrile [1.3 g, Κί = 0.2 (1: 1

- 39 016912

EA / heptane)] is obtained using a procedure similar to that described in Example 1, parts a and b, except that the starting material is 4,5,7-trichloro-1H-benzotriazole. 4,5,7-Trichloro-1Nbenzotriazole (4 g, 85%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 2-nitro-3,4,6-trichloroaniline ( 6.1 g), which is prepared as follows.

a. 2,4,5-Trichloroaniline (10 g) was dissolved in acetic anhydride (50 ml) and stirred overnight at room temperature. The resulting solid was filtered off and dried to give Y- (2,4,5-trichlorophenyl) acetamide as a grayish-white solid (12 g, 99%). Κί = 0.5 (1: 1 EA / heptane).

b. To a solution of L- (2,4,5-trichlorophenyl) acetamide (12 g) in concentrated sulfuric acid (50 ml) at 0 ° C, concentrated nitric acid (8 ml) was added dropwise. After the addition was completed, the mixture was allowed to slowly warm to room temperature. After 5 hours, the mixture was poured into ice water (200 ml). The resulting solid is filtered off, washed with water and crystallized from a mixture of water and ethanol. The resulting solid was filtered and dried to obtain Y- (2-nitro-3,4,6-trichlorophenyl) acetamide as a gray solid (12 g, 99%).

c. A solution of L- (2-nitro-3,4,6-trichlorophenyl) acetamide (7 g) in dioxane and concentrated hydrochloric acid (70 ml) was heated and refluxed overnight. The mixture was concentrated under reduced pressure to remove dioxane, diluted with water (150 ml), neutralized with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain 2-nitro-3,4,6-trichloroaniline as a gray solid (6.1 g, quantitative yield). W = 0.6 (3: 7 EA / heptane).

Example 40. M- [1-Cyano-1-methyl-2- (4,5,7-trichloro-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.065).

When using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (4,5,7-trichloro-2H-benzotriazol-2-yl) propionitrile (150 mg described in example 39) and 4 trifluoromethylthiobenzoyl chloride (0.1 ml), the title compound is isolated as a white solid (200 mg, 80%). W = 0.55 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 508. NMR: (400 MHz, DMSO-b ₆ ): 1.76 (s, 3H), 5.45 (d, 4 = 13.3 Hz, 1H), 5.61 (d, 1 = 13.3 Hz, 1H), 7.83-7.92 (m, 4H), 7.94 (s, 1H) and 8.91 (s, 1H). ¹⁹ G NMR (376 MHz, DMSO-b ₆ ): -42.0 (s, 3G).

Example 41. N- [1-Cyano-1-methyl-2- (4,5,7-trichloro-2H-benzotriazol-2-yl) ethyl] -4- (1,2,2,2-tetrafluoroethyl) benzamide (Compound No. 1.069).

Using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (4,5,7-trichloro-2H-benzotriazol-2-yl) propionitrile (35 mg, described in example 39) and 4 - (1,2,2,2-tetrafluoroethyl) benzoyl chloride, the title compound is isolated as a solid (6.2 mg, 11%). MS (ES): M / Ζ [M + H] = 508. NMR: (400 MHz, chloroform-b): 1.90 (s, 3H), 5.20 (d, 1 = 13.8 Hz, 1H), 5.53 (d, 1 = 13.8 Hz, 1H ), 5.69 (dq, 1 = 44.3 Hz, 5.9 Hz, 1H), 7.54 (br s, 1H), 7.58 (s, 1H), 7.60 (d, 1 = 8.1 Hz, 2H) and 7.98 (d, 1 = 8.2 Hz, 2H). ¹⁹ g NMR (376 MHz, chloroform-b); -197.6 - -197.1 (m, 1G), -79.0 (q, 1 = 5.9 Hz, 3G).

4- (1,2,2,2-Tetrafluoroethyl) benzoyl chloride is prepared as follows.

a. To a solution of 4-formylbenzoic acid methyl ester (4 g) in THF (40 ml) was added a solution of tetrabutylammonium fluoride (1 M in THF, 2.4 ml), followed by a solution of (trifluoromethyl) trimethylsilane (2 M in THF, 13.4 ml ) Water was added to suppress the reaction and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain a residue which was purified by chromatography (8ίΟ _2, heptane / EA) to give methyl 4- (2,2,2-trifluoro-1-hydroxyethyl) benzoate (4.5 g, 78%). ¹ H NMR: (400 MHz, DMSO-b6): 3.86 (s, 3H), 5.30 (m, 1H), 7.01 (d, 1 = 5.7 Hz, 1H), 7.65 (d, 1 = 8.2 Hz, 2H), 8.00 (d, 1 = 8.4 Hz, 2H). ¹⁹ G NMR (376 MHz, DMSO-b6): -77.0 (d, 1 = 7.3 Hz, 3G).

b. To a cooled solution of 4- (2,2,2-trifluoro-1-hydroxyethyl) benzoic acid methyl ester (0.94 g) in DCM (9 ml) was added (diethylamino) sulfotrifluoride (1.2 ml). The mixture was allowed to slowly warm to room temperature overnight. Water was added and the mixture was extracted with additional DCM. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain 4- (1,2,2,2-tetrafluoroethyl) benzoic acid methyl ester (0.94 g, 99%). ¹ H NMR: (400 MHz, DMSO-b6): 3.88 (s, 3H), 6.52 (m, 1H), 7.69 (d, 1 = 8.2 Hz, 2H), 8.09 (d, 1 = 8.1 Hz, 2H). ¹⁹ G NMR (376 MHz, DMSO-b6): -197.9 (m, 1G), -78.0 (m, 3G).

c. A mixture of 4- (1,2,2,2-tetrafluoroethyl) benzoic acid methyl ester (190 mg) and lithium hydroxide (19 mg) in methanol and water was stirred at room temperature overnight. The mixture was slightly acidified with a solution of 6 N hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain 4- (1,2,2,2-tetrafluoroethyl) benzoic acid (86 mg, 48%). ¹ H NMR: (400 MHz, DMSO-b ₆ ): 6.50 (m, 1H), 7.65 (d, 1 = 8.2 Hz, 2H), 8.07 (d, 1 = 8.0 Hz, 2H), 13.43 (br s, 1H). ¹⁹ g NMR (376

- 40 016912

MHz, DMSO-b ₆ ): -199.0 - -196.4 (m, 1G), -78.0 (m, 3G).

b. Oxalyl chloride (0.13 ml) was added to 4- (1,2,2,2-tetrafluoroethyl) benzoic acid (96 mg) in DCM (5 ml) and dimethylformamide (0.2 ml). After 4 hours at room temperature, the mixture was concentrated under reduced pressure to obtain 4- (1,2,2,2-tetrafluoroethyl) benzoyl chloride.

Example 42. No. [2- (4-Chloro-6-methoxy-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.070).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (4-chloro-6-methoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile (50 mg), the title compound was isolated as solid white substances (87 mg, 88%). MS (ES): M / Ζ [M + H] = 454. ¹ H NMR: (400 MHz, dichloromethane-b2): 1.86 (s, 3H), 3.88 (s, 3H), 5.11 (d, 1 = 13.9 Hz, 1H), 5.35 (d, 1 = 13.9 Hz, 1H), 7.05 (d, 1 = 2.1 Hz, 1H), 7.20 (d, 1 = 2.0 Hz, 1H), 7.34 (d , 1 = 8.1 Hz, 2H), 7.67 (s, 1H) and 7.93 (d, 1 = 8.8 Hz, 2H). ¹⁹ G NMR (376 MHz, dichloromethane-b2): -58.5 (s, 3G).

2-amino-3- (4-chloro-6-methoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile was prepared using the procedure similar to that described in example 1, parts a and b, except that the starting material is 7-chloro-5-methoxy-1H-benzotriazole. 7-Chloro-5-methoxy-1H-benzotriazole (0.8 g) was obtained using the procedure similar to that described in example 13, part a, except that the starting material was 3-chloro-1,2-diamino-5 methoxybenzene. 3-Chloro-1,2-diamino-5-methoxybenzene (1.88 g, 75%) was obtained using the procedure similar to that described in example 38, part a and b, except that the starting material was 4-methoxy-2- nitroaniline (16.8 g) and Ν-chlorosuccinimide (15 g) in part a to obtain 6-chloro-4-methoxy-2-nitroaniline (2.9 g, 14%) used in part b.

Example 43. No. [2- (4-Chloro-6-methoxy-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.071).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (4-chloro-6-methoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile (50 mg, described in example 42) and 4- trifluoromethylthiobenzoyl chloride (0.04 ml), the title compound is isolated as a white solid (45 mg, 51%). MS (ES): M / Ζ [M + H] = 470. ¹ H NMR: (400 MHz, dichloromethane-b ₂ ): 1.86 (s, 3H), 3.88 (s, 3H), 5.11 (d, 1 = 13.9 Hz, 1H), 5, 36 (d, 1 = 13.9 Hz, 1H), 7.05 (d, 1 = 2.1 Hz, 1H), 7.20 (d, 1 = 2.0 Hz, 1H),

7.72 (s, 1H), 7.79 (d, 1 = 8.2 Hz, 2H) and 7.92 (d, 1 = 8.6 Hz, 2H). ¹⁹ g NMR (376 MHz, dichloromethane-b ₂ ): -42.8 (s,

3G).

Example 44. No. [1-cyano-2- (5-methoxy-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.072).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (5-methoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile (150 mg), the title compound was isolated as a white solid (190 mg , 70%). Κί = 0.35 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 420. ^! H NMR: (400 MHz, DMSO-b6): 1.73 (s, 3H), 3.84 (s, 3H), 5.32 (d, 1 = 13.4 Hz, 1H), 5.37 ( d, 1 = 13.4 Hz, 1H), 7.10 (dd, 1 = 9.3, 2.1 Hz, 1H), 7.24 (d, 1 = 2.1 Hz, 1H), 7, 52 (d, 1 = 8.1 Hz, 2H), 7.82 (dd, 1 = 9.3, 0.4 Hz, 1H), 7.95 (d, 1 = 8.9 Hz, 2H) and 8.92 (s, 1H). ¹⁹ G NMR (376 MHz, DMSO-b6): -57.1 (s, 3G).

2-amino-3- (5-methoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile was obtained using the procedure similar to that described in example 1, part a and b, except that the starting material was 5-methoxy -1H-benzotriazole, which is prepared as follows.

a. To a solution of 1,2-diamino-4-methoxybenzene hydrochloride (2 g) in acetonitrile (20 ml) was added dropwise tert-butyl nitrite (1.35 ml) at 0 ° C. After 4 hours at room temperature, the mixture was concentrated under reduced pressure to obtain a solid residue, which was then dissolved in water. The aqueous solution was neutralized with saturated sodium bicarbonate and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain 5methoxy-1H-benzotriazole as a grayish-white solid (1.2 g, 85%). MS (ES): M / Ζ [M + H] = 150.

Example 45. N- [1-Cyano-2- (5-methoxy-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.073).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-methoxy-2H-benzotriazol-2-yl) -2-methylpropionitrile (120 mg, described in example 44) and 4-trifluoromethylthiobenzoyl chloride (0, 16 ml), the title compound was isolated as a white solid (150 mg, 66%). Κί = 0.3 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 436. Ή NMR: (400 MHz, DMSO ₆ ): 1.73 (s, 3H), 3.84 (s, 3H), 5.32 (d, 1 = 13.4 Hz, 1H), 5.38 (d , 1 = 13.4 Hz, 1H), 7.10 (dd, 1 = 9.3, 2.3 Hz, 1H), 7.24 (d, 1 = 2.1 Hz, 1H), 7.82 (dd, 1 = 9.2, 0.4 Hz, 1H), 7.87 (d, 1 = 8.6 Hz, 2H), 7.92 (d, 1 = 8.6 Hz, 2H) and 9 , 00 (s, 1H). ¹⁹ G NMR (376 MHz, DMSO-b ₆ ): -41.9 (s, 3G).

Example 46. No. [1-Cyano-2- (5,7-dichloro-4-fluoro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.090).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5,7-dichloro-4-fluoro-2H-benzotriazol-2-yl) -2-methylpropionitrile (90 mg), title compound

- 41 016912 is isolated as a white solid (65 mg, 44%). W = 0.6 (1: 1 EA / heptane). MS (ES): Μ / Ζ [M + H] = 476. ¹ H NMR: (400 MHz, DMSO-b6): 1.76 (s, 3H), 5.47 (d, 1 = 13.3 Hz, 1H), 5.58 (d, 1 = 13.4 Hz , 1H), 7.50 (d, 1 = 8.1 Hz, 2H), 7.70-8.10 (m, 3H) and 8.86 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -127.6 (d, 1 = 5.9 Hz, 1P) and -57.1 (s, 3P).

2-amino-3- (5,7-dichloro-4-fluoro-2H-benzotriazol-2-yl) -2-methylpropionitrile [1.3 g, IG = 0.2 (1: 1 EA / heptane)] was obtained using a procedure similar to that described in Example 1, parts a and b, except that the starting material was 5,7-dichloro-4-fluoro-1H-benzotriazole. 5,7-Dichloro 4-fluoro-1H-benzotriazole (4 g, 85%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 4,6-dichloro-3-fluoro- 2 nitroaniline. 4,6-Dichloro-3-fluoro-2-nitroaniline (6.1 g) was obtained using the procedure similar to that described in example 39, parts a, b and c, except that the starting material was 2,4dichloro-5 fluoroaniline (10 g).

Example 47. Y- [1-Cyano-2- (5,7-dichloro-4-fluoro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.091).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (5,7-dichloro-4-fluoro-2H-benzotriazol-2-yl) -2-methylpropionitrile (90 mg, described in example 46) and 4-trifluoromethylthiobenzoyl chloride (0.06 ml), the title compound was isolated as a white solid (95 mg, 62%). HB = 0.55 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 492. NMR: (400 MHz, DMSO ₆ ): 1.76 (s, 3H), 5.47 (d, 1 = 13.3 Hz, 1H), 5.60 (d, 1 = 13.3 Hz, 1H) 7.58-8.22 (m, 5H); and 8.94 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -127.6 (d, 1 = 5.3 Hz, 1P) and -42.0 (s, 3P).

Example 48. Y- [2- (5-Chloro-4,7-dimethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.092).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (5chloro-4,7-dimethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (120 mg), the title compound was isolated as a white solid substances (85 mg, 41%). W = 0.7 (1: 1 EA / heptane). MS (ES): Μ / Ζ [M + H] = 452. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.74 (s, 3H), 2.43 (s, 3H), 2.45 (s, 3H), 5.35 (d, 1 = 13 , 3 Hz, 1H),

5.52 (d, 1 = 13.3 Hz, 1H), 7.25 (d, 1 = 0.6 Hz, 1H), 7.51 (d, 1 = 8.1 Hz, 2H), 7, 91 (d, 1 = 8.8 Hz, 2H) and 8.78 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -57.2 (s, 3P).

2-amino-3- (5-chloro-4,7-dimethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile [1.3 g, KG = 0.2 (1: 1 EA / heptane)] get using a procedure similar to that described in example 1, parts a and b, except that the starting material is 5-chloro-4,7-dimethyl-1H-benzotriazole. 5-Chloro-4,7dimethyl-1H-benzotriazole (4 g, 85%) was obtained using the procedure similar to that described in example 11, part a, except that the starting material was 4-chloro-3,6-dimethyl- 2 nitroaniline. 4-Chloro-3,6-dimethyl-2-nitroaniline (6.1 g) was obtained using the procedure similar to that described in example 39, parts a, b and c, except that the starting material was 4dichloro-2,5 dimethylaniline (10 g).

Example 49. Y- [2- (5-Chloro-4,7-dimethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.092).

When using a procedure similar to that described in example 1, except for the use of 2amino-3- (5chloro-4,7-dimethyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (120 mg described in example 48) and 4- trifluoromethylthiobenzoyl chloride (0.09 ml), the title compound is isolated as a white solid (180 mg, 85%). BP = 0.7 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 468. NMR: (400 MHz, DMSO-b ₆ ): 1.74 (s, 3H), 2.43 (s, 3H), 2.44 (s, 3H), 5.34 (d, 1 = 13.3 Hz, 1H), 5.54 (d, 1 = 13.3 Hz, 1H), 7.24 (d, 1 = 0.7 Hz, 1H), 7.81-7.93 (m, 4H) and 8.86 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.1 (s, 3P).

Example 50. Y- [2- (5-Bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.094).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (120 mg), the title compound was isolated as a white solid (130 mg, 68%). W = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 500. ¹ H NMR: (400 MHz, DMSO-b6): 1.75 (s, 3H), 2.42 (s, 3H), 5.40 (d, 1 = 13.3 Hz, 1H), 5.54 (d, 1 = 13.4 Hz, 1H), 7.45 (d, 1 = 5.7 Hz, 1H), 7.51 (d, 1 = 8.3 Hz, 2H), 7.91 (d , 1 = 8.7 Hz, 2H) and 8.82 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -122.4 (d, 1 = 5.3 Hz, 1P) and -57.1 (s, 3P).

2-amino-3- (5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile [1.3 g, W = 0.2 (1: 1 EA / heptane) ] are obtained using a procedure similar to that described in Example 1, parts a and b, except that the starting material is 5-bromo-4-fluoro-7-methyl-1H-benzotriazole. 5-Bromo-4-fluoro-7-methyl-1H-benzotriazole (4 g, 85%) was obtained using a procedure similar to that described in example 11, part a, except that the starting material was 4-bromo-3-fluoro- 6-methyl-2 nitroaniline. 4-Bromo-3-fluoro-6-methyl-2-nitroaniline (6.1 g) was obtained using the procedure similar to that described in example 39, parts a, b and c, except that the starting material was 4-bromo. -5-fluoro-2-methylaniline (10 g).

- 42 016912

Example 51. No. [2- (5-Bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.095).

Using a procedure similar to that described in example 1, except for using 2amino-3- (5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (120 mg, described in example 50 ) and 4-trifluoromethylthiobenzoyl chloride (0.09 ml), the title compound is isolated as a white solid (175 mg, 88%). Κί = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 516. NMR: (400 MHz, DMSO-4 ₆ ): 1.75 (s, 3H), 2.41 (s, 3H), 5.41 (d, 1 = 13.3 Hz, 1H), 5.56 ( d, 1 = 13.3 Hz, 1H), 7.45 (dd, 1 = 5.9, 1.1 Hz, 1H), 7.85-7.90 (m, 4H), 8.90 (s , 1H). ¹⁹ P NMR (376 MHz, DMSO-4 ₆ ): -122.4 (d 1 = 5.3 Hz, 1P), -42.0 (s, P).

Example 52. No. [2- (4-Bromo-5-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.057).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (4-bromo-5-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (48 mg), the title compound was isolated as a white solid substances (43 mg, 56%). MS (ES): M / Ζ [M + H] = 502. ¹ H NMR: (400 MHz, DMSO-46): 1.75 (s, 3H), 5.42 (d, 1 = 13.4 Hz, 1H), 5.54 (d, 1 = 13.4 Hz , 1H), 7.51 (d, 1 = 8.1 Hz, 2H), 7.63 (d, 1 = 9.0 Hz, 1H), 7.93 (d, 1 = 8.8 Hz, 2H ), 8.02 (d, 1 = 9.0 Hz, 1H) and 8.88 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-46): -57.1 (s, 3P).

2-amino-3- (4-bromo-5-chloro-2H-benzotriazol-2-yl) -2-methylpropionitrile (48 mg) was obtained using the procedure similar to that described in example 1, part a and b, except that the starting material is 4-bromo-5-chloro-1H-benzotriazole (213 mg), which is prepared as follows.

a. To a solution of 5-chloro-1H-benzotriazole (213 mg) and sodium acetate (1g) in acetic acid was added bromine (2 g). After 10 days at room temperature, the mixture is treated with saturated sodium thiosulfate solution, neutralized with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, filtered and the filtrate is concentrated under reduced pressure to obtain a residue which is purified by semi-preparative liquid chromatography to obtain 4-bromo-5-chloro-1H-benzotriazole as a grayish-white solid (213 mg, 14%). MS (ES): M / Ζ [M + H] = 232. Ή NMR: (400 MHz, DMSO-4 ₆ ): 7.58 (d, 1 = 8.7 Hz, 2H) and 7.91 (d, 1 = 8.7 Hz, 1H).

Example 53. No. [2- (5-Chloro-4,7-dibromo-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.083).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-chloro-4,7-dibromo-2H-benzotriazol-2-yl) -2-methylpropionitrile (390 mg), the title compound was isolated as white solid (530 mg, 90%). MS (ES): M / Ζ [M + H] = 580. ¹ H NMR: (400 MHz, DMSO-46): 1.75 (s, 3H), 5.43 (d, 1 = 13.3 Hz, 1H), 5.59 (d, 1 = 13.4 Hz , 1H), 7.51 (d, 1 = 8.0 Hz, 2H), 7.847.96 (m, 2H), 8.04 (s, 1H) and 8.83 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-46): -57.1 (s, 3P).

2-amino-3- (5-chloro-4,7-dibromo-2H-benzotriazol-2-yl) -2-methylpropionitrile (440 mg) was obtained using a procedure similar to that described in example 1, part a and b, for except that the starting material is 5-chloro-4,7-dibromo-1H-benzotriazole, which is obtained using the procedure described in the literature by K. Korapka e! a1. in Vuogudas & Me4yut1 SRetBBu, uo1. 13 (2005), p. 3601 and in Vuoguds & Me4yut1 SRETSCHBU, wo1. 12 (2004), p. 2617-2624.

a. To a solution of 5-chloro-1H-benzotriazole (7.7 g) and silver sulfate (19 g) in sulfuric acid (100 ml), bromine (15 ml) is slowly added. After standing for two days at room temperature, water was slowly added to the cooled mixture, and the mixture was stirred at room temperature for 3 days. The resulting solid was filtered off, washed with water and triturated with ethyl acetate. The organic filtrate was collected and treated with a saturated solution of sodium bisulfite, then with water, dried over anhydrous sodium sulfate and filtered through a layer of CeSe®. The filtrate was concentrated under reduced pressure to obtain 5-chloro-4,7-dibromo-1H-benzotriazole as a solid (11.2 g, 71%). MS (ES): M / Ζ [M + H] = 310. ¹ H NMR: (400 MHz, DMSO-4 ₆ ): 8.0 (s, 1H).

Example 54. No. [2- (5-Chloro-4,7-dibromo-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.085).

When using a procedure similar to that described in example 1, except for the use of 2 amino-3- (5-chloro-4,7-dibromo-2H-benzotriazol-2-yl) -2-methylpropionitrile (44 mg, described in example 53) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (15 mg, 22%). MS (ES): M / Ζ [M-H] = 594. NMR: (400 MHz, DMSO-4 ₆ ): 1.75 (s, 3H), 5.43 (d, 1 = 13.4 Hz, 1H), 5.61 (d, 1 = 13.3 Hz, 1H), 7.88 (q, 1 = 8.5 Hz, 4H), 8.04 (s, 1H) and 8.91 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-46): -42.0 (s, 3P).

Example 55. No. [2- (4-Bromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.086).

Using a procedure similar to that described in Example 1, except for using 2amino-3- (4-bromo-5,7-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound

- 43 016912 divided as a white solid (260 mg). MS (ES): M / Ζ [M + H] = 536. ¹ H NMR: (400 MHz, DMSOph): 1.76 (s, 3H), 5.44 (d, 1 = 13.2 Hz, 1H), 5.59 (d, 1 = 13.4 Hz, 1H ), 7.51 (d, 1 = 8.1 Hz, 2H), 7.84-7.99 (m, 3H) and 8.83 (s, 1H). ¹⁹ E NMR (376 MHz, DMSOD ₆ ): -57.1 (s, 3E).

2-amino-3- (4-bromo-5,7-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile was prepared using a procedure similar to that described in example 1, parts a and b, except that the starting material is 4-bromo-5,7-dichloro-1H-benzotriazole, which is obtained together with 4,6-dibrom-5,7-dichloro-1H-benzotriazole, using a procedure similar to that described in example 53, excluding the use of 5,7-dichloro-1H-benzotriazole described in example 15.

Example 56. No. [2- (4-Bromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylbenzamide (compound No. 1.087).

Using a procedure similar to that described in example 1, except for the use of 2 amino-3- (4-bromo-5,7-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile and 4-trifluoromethylthiobenzoyl chloride, the title compound was isolated as white solid (110 mg described in example 55). MS (ES): M / Ζ [M + H] = 552. NMR: (400 MHz, DMSOD ₆ ): 1.75 (s, 3H), 5.44 (d, 1 = 13.3 Hz, 1H), 5.60 (d, 1 = 13.7 Hz, 1H) 7.75-8.04 (m, 5H); and 8.91 (s, 1H). ¹⁹ E NMR (376 MHz, DMSOD ₆ ): -42.0 (s, 3E).

Example 57. No. [1-Cyano-2- (4,6-dibromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.088).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (4,6-dibromo-5,7-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile, the title compound was isolated as a white solid substances (130 mg). MS (ES): M / Ζ [M + H] = 614. ¹ H NMR: (400 MHz, DMSO): 1.75 (s, 3H), 5.45 (d, 1 = 13.3 Hz, 1H), 5.59 (d, 1 = 13.4 Hz, 1H ), 7.51 (d, 1 = 8.0 Hz, 2H), 7.91 (d, 1 = 8.8 Hz, 2H) and 8.82 (s, 1H). ¹⁹ B NMR (376 MHz, DMSOD ₆ ): -57.1 (s, 3E).

2-amino-3 - (4,6-dibromo-5,7-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile was prepared using a procedure similar to that described in example 1, parts a and b, except that the starting material is 4,6-dibromo-5,7-dichloro-1H-benzotriazole, which was prepared together with 4-bromo-5,7-dichloro-1H-benzotriazole described in Example 55 using the procedure similar to that described in example 53, except for the use of 5,7-dichloro-1H-benzotriazole described in example 15.

Example 58. No. [1-Cyano-2- (4,6-dibromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4 trifluoromethylthiobenzamide (compound No. 1.089).

Using a procedure similar to that described in example 1, except for using 2amino-3- (4,6-dibromo-5,7-dichloro-2H-benzotriazol-2-yl) -2-methylpropionitrile described in examples 57 and 4- trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (100 mg). MS (ES): M / Ζ [M + H] = 630. NMR: (400 MHz, DMSOD ₆ ): 1.75 (s, 3H), 5.45 (d, 1 = 13.3 Hz, 1H), 5.60 (d, 1 = 13.0 Hz, 1H) 7.82-7.92 (m, 4H); and 8.90 (s, 1H). ¹⁹ E NMR (376 MHz, DMSOD ₆ ): -42.0 (s, 3E).

The compounds of examples 59 and 60 were obtained according to the following general reaction scheme:

Final product:

V = CH; No. = C-C1; X = CH;

Ο = Γ = Ν;

K ₃ = K ₄ = H; a = 1; K ₅ = CH ₃ ; K ₆ = H;

Ζ = 6 (Ό); K ₇ = p-phenyl-K.

Example 59. No. [2- (6-Chloro-4-vinyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.075).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (2.3 g), the title compound was isolated as white solid (3.2 g, 80%). KG = 0.45 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 450. Ή NMR: (400 MHz, DMSOD ₆ ): 1.75 (s, 3H), 5.41 (d, 1 = 13.3 Hz, 1H), 5.51 (dd, 1 = 11.2, 1, 2 Hz, 1H), 5.55 (d, 1 = 13.4 Hz, 1H), 6.45 (dd, 1 = 17.7, 1.2 Hz, 1H), 6.91 (dd, 1 = 17.6, 11.3 Hz, 1H), 7.48-7.52 (m, 3H), 7.93 (d, 1 = 8.8 Hz, 2H), 8.03 (d, 1 = 1 8 Hz, 1H) and 8.87 (s, 1H). ¹⁹ E NMR (376 MHz, DMSOD ₆ ): -57.1 (s, 3E).

2-amino-3- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) -2-methylpropionitrile [2.3 g 97%, KG = 0.3 (1: 1 EA / heptane)] get using a procedure similar to that described in example 1, parts a and b, for

- 44 016912 except that the starting material is 1- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) propan-

2-he. 1- (6-Chloro-4-vinyl-2H-benzotriazol-2-yl) propan-2-one (4 g, 85%) was prepared as follows.

a. 1- (4-Bromo-6-chloro-2H-benzotriazol-2-yl) -propan-2-one (3 g), tributyl vinyltin (3.5 g) and bis (tri-tert-butylphosphine) palladium (0, 5 g) are heated in toluene (20 ml) at 50 ° C. overnight. The mixture was concentrated under reduced pressure, transferred to ethyl acetate and filtered through a Ce1be® layer. The filtrate was concentrated under reduced pressure to obtain a residue which was purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) propan-2-one as white solid (2.2 g, 90%). KG = 0.5 (1: 1 EA / heptane). 1- (4-Bromo-6-chloro-2H-benzotriazol2-yl) propan-2-one is obtained using a procedure similar to that described in example 1, parts a and b, except that the starting material is 7 β-bromo-5-chloro-1H-benzotriazole described in Example 38, parts a and b.

Example 60. Y- [2- (6-Chloro-4-vinyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.076).

Using a procedure similar to that described in example 1, except for the use of 2 amino-3- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) -2-methylpropionitrile (50 mg) described above in example 59, and 4 trifluoromethylthiobenzoyl chloride (0.05 ml), the title compound is isolated as a white solid (65 mg, 73%). KG = 0.5 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 466. NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.41 (d, 1 = 13.4 Hz, 1H), 5.50 (d, 1 = 11.5 Hz, 1H), 5.57 (d, 1 = 13.4 Hz, 1H), 6.45 (d, 6 = 17.6 Hz, 1H), 6.91 (dd, 1 = 17.6, 11.3 Hz, 1H), 7.51 (s, 1H), 7.84 (d, 1 = 8.2 Hz, 2H), 7.91 (d, 1 = 8.3 Hz, 2H), 8.03 ( s, 1H) and 8.96 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.0 (s, 3P).

The compounds of examples 61-67 obtained according to the following General reaction scheme:

Final product:

ν ^ -4; No. = C-C1; X = CH; Υ = € -Β _η ;

Kc = CO ₂ H, CO ₂ Me, CH ₂ K (CH ₃ ) 2, CH ₂ OH, CH (OH) CH ₂ OH, CHRS ₂ P;

Ο = Ρ = Ν;

K3 = K4 = H; a = 1; K5 = CH3; K6 = H;

Ζ = Ο (Ό); K ₇ = p-phenyl-OCP ₃ .

Example 61. Ν- {2- | 6-Chloro-4- (1,2-dihydroxyethyl) -2H-benzotriazol-2-yl] -1-cyano-1-methylethyl} -4 trifluoromethoxybenzamide (compound No. 1.077).

To a solution of Y- [2- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (0.25 g) in 5 ml of a mixture of THF and water (10: 1) sodium periodate (0.24 g, 2.1 eq) and a 4% solution of osmium tetroxide in water (17 ml, 5 mol%) are added. After 2 hours at room temperature, the reaction was quenched with a 10% solution, extracted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA), to obtain the title compound as a white solid mixture of diastereoisomers (110 mg, 40%). KG = 0.35 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 484. ^! H NMR: (400 MHz, DMSO-b ₆ ): 1.74-1.75 (d, 3H), 3.40-3.56 (m, 1H), 3.67-3.82 (m, 1H ), 4.78 (dt, 1 = 17.3, 6.0 Hz, 1H), 5.01-5.12 (m, 1H), 5.35-5.43 (m, 1H), 5, 43-5.51 (m, 1H), 5.61 (d, 1 = 4.8 Hz, 1H), 7.42 (s, 1H), 7.51 (d, 1 = 7.9 Hz, 2H ), 7.93 (dd, 1 = 8.7, 3.8 Hz, 2H), 7.98 (t, 1 = 2.1 Hz, 1H) and 8.92 (d, 1H). ¹⁹ P NMR (376

- 45 016912

MHz, DMSO-b6): -57.1 (s, 3P).

Example 62. N- {2- [6-Chloro-4- (1,2-difluoroethyl) -2Η-benzotriazol-2-yl] -1-cyano-1-methylethyl} -4 trifluoromethoxybenzamide (compound No. 1.078).

To a solution of N- {2- [6-chloro-4- (1,2-dihydroxyethyl) -2Η-benzotriazol-2-yl] -1-cyano-1-methylethyl} -4 trifluoromethoxybenzamide (50 mg) in DCM (3 ml ) add EsohoPiog ™ [bis (2-methoxyethyl) aminotrifluoride sulfur] (0.07 ml). After stirring overnight at room temperature, the mixture was concentrated under reduced pressure to obtain a residue which was purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound as a white solid mixture of diastereoisomers (35 mg, 69%). KR = 0.7 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 488. Ή NMR: (400 MHz, chloroform-b): 1.88-1.89 (d, 3H), 4.71-5.00 (m, 2H), 5.19 (dd, 1 = 13.7, 4.5 Hz, 1H), 5.47 (t, 1 = 13.9 Hz, 1H), 5.99-6.25 (m, 1H), 7.20 (d, 1 = 18.7 Hz, 1H), 7.33 (d, 1 = 8.1 Hz, 2H), 7.53 (s, 1H), 7.86 (d, 1 = 8.7 Hz, 2H) and 7.90 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -192.2 (s, 1P), -58.1 (s, 3P) and 3.1 (broad s, 1P).

Example 63. N- [2- (6-Chloro-4-formyl-2Η-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.079)

A solution of Ν- [2 - (6-chloro-4-vinyl-2H-benzotriazole-2-yl) - 1-cyano -1-methylethyl] -4 trifluoromethoxybenzamide (0.29 g) in 35 ml of a mixture of DCM and methanol (3: 1) is treated with gaseous ozone for 15 minutes After stirring for 1 h at -78 ° C, the mixture was purged with oxygen for 10 min and then quenched with dimethyl sulfide and then with 10% sodium thiosulfate solution and diluted with DCM (100 ml). The mixture was separated and the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue which was purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound as a white solid (0.23 g, 79%) . KR = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 452. Ή NMR: (400 MHz, chloroform-b): 1.58 (s, 3H), 5.24 (d, 1 = 13.8 Hz, 1H), 5.47 (d, 1 = 13.8 Hz, 1H), 7.37 (d, 1 = 8.1 Hz, 2H), 7.94 (br s, 1H), 8.00 (d, 1 = 1.8 Hz, 1H), 8.05 (m , 2H), 8.22 (d, 1 = 1.9 Hz, 1H) and 10.34 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s 3P).

Example 64. N- [2- (6-Chloro-4-dimethylaminomethyl-2Η-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.080).

To a solution of N- [2- (6-chloro-4-formyl-2Η-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (0.18 g) in methanol (3 ml) was added 2 M methanol solution of dimethylamine (0.24 ml). After stirring for 1 h at room temperature, decaborane (15 mg) was added and the mixture was stirred for another 1 h before concentration under reduced pressure. The residue was purified by chromatography (81O ₂ , heptane / EA) to give the title compound as a white solid (100 mg, 52%). KR = 0.2 (3: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 481. Ή NMR: (400 MHz, chloroform-b): 1.81 (s, 3H), 2.31 (s, 6H), 3.75 (d, 1 = 13.5 Hz, 1H), 3.92 ( d, 1 = 13.5 Hz, 1H), 5.12 (d, 1 = 13.8 Hz, 1H),

5.52 (d, 1 = 13.7 Hz, 1H), 7.32 (d, 1 = 8.1 Hz, 2H), 7.36 (s, 1H), 7.81 (d, 1 = 1 7 Hz, 1H) and 7.95 (broad d, 1 = 8.7 Hz, 3H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

Example 65. N- [2- (6-Chloro-4-hydroxymethyl-2Η-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.081).

To a solution of N- [2- (6-chloro-4-formyl-2Η-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (150 mg) in ethanol (2 ml), cooled in an ice bath, sodium triacetoxyborohydride (0.22 g) was added. After 6 hours at room temperature, another 0.29 g of sodium triacetoxyborohydride was added and the mixture was stirred overnight at room temperature. The mixture was quenched with water, extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA), to obtain the title compound as a white solid (100 mg, 67%). KR = 0.4 (3: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 454. Ή NMR: (400 MHz, chloroform-b): 1.87 (s, 3H), 5.06 (s, 2H), 5.15 (d, 1 = 13.8 Hz, 1H), 5.43 ( d, 1 = 13.8 Hz, 1H), 7.33 (d, 1 = 8.8 Hz, 2H), 7.43 (dt, 1 = 1.8, 1.0 Hz, 1H), 7, 47 (s, 1H), 7.80 (d, 1 = 1.8 Hz, 1H) and 7.88 (d, 1 = 8.8 Hz, 2H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

Example 66. 6-Chloro-2- [2-cyano-2 - ({[4- (trifluoromethoxy) phenyl] carbonyl} amino) propyl] -2Nbenzotriazole-4-carboxylic acid (compound No. 1.082).

To a solution of N- [2- (6-chloro-4-formyl-2Η-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (1.5 g) in a mixture of THF (25 ml) , tert-butanol (10 ml) and 2-methyl-2-butene are added dropwise a solution of sodium hypochlorite (0.9 g) and sodium dihydrogen phosphate (1.15 g) in water (20 ml). After 4 hours at room temperature, the mixture was concentrated under reduced pressure, diluted with water (50 ml) and acidified to pH 2 with normal HCl. The white solid was filtered off, washed with water and dried in vacuo to give the title compound (1.35 g, 87%). MS (ES): M / Ζ [M + H] = 468. ¹ H NMR: (400 MHz, DMSO-b6): 1.72 (s, 3H), 5.48-5.64 (m, 2 H), 7.43 (d, 1 = 8.2 Hz, 2H ), 7.83 (d, 1 = 2.0 Hz, 1H), 7.99 (d, 1 = 8.8 Hz, 2H), 8.23 (d, 1 = 1.8 Hz, 0H) and 9.41 (br s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

Example 67. 6-Chloro-2- [2-cyano-2 - ({[4- (trifluoromethoxy) phenyl] carbonyl} amino) propyl] -2H-benzotriazole-4-carboxylic acid methyl ester (compound No. 1.084).

M ethereal solution of trimethylsilyldiazomethane is added to 6-chloro-2- [2-cyano-2 - ({[4

- 46 016912 (trifluoromethoxy) phenyl] carbonyl} amino) propyl] -2H-benzotriazole-4-carboxylic acid (100 mg) dissolved in a mixture (10: 1, 2 ml) of THF and methanol. After standing overnight at room temperature, the mixture was concentrated under reduced pressure to give the title compound as a white solid (42 mg, 40%). MS (ES): M / Ζ [M + H] = 482. ¹ H NMR: (400 MHz, DMSO-b6): 1.75 (s, 3H), 3.78 (s, 3H), 5.44 (d, 1 = 13.3 Hz, 1H), 5.58 (d, 1 = 13.3 Hz, 1H), 7.50 (d, 1 = 8.1 Hz, 2H), 7.92 (d, 1 = 8.8 Hz, 2H), 8.02 (d , 1 = 1.9 Hz, 1H), 8.52 (d, 1 = 1.9 Hz, 1H) and 8.87 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

The preparation of 6-chloro-2- [2-cyano-2 - ({[[4- (trifluoromethoxy) phenyl] carbonyl} amino) propyl] -2H-benzotriazole-4-carboxylic acid is described in Example 66 above.

The compound of example 68 was obtained according to the following general reaction scheme:

Final product:

ν ^ -4; No. = C-C1; X = CH; Υ = C-CH ₂ NH ₂ ;

OR Ν;

K ₃ = H4 = H; a = 1; K ₅ = CH ₃ ; K ₆ = H;

Ζ = 0 (Ό); K ₇ = p-phenyl-K.

Example 68. No. [2- (4-Aminomethyl-6-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.074).

To a solution of {6-chloro-2- [2-cyano-2-methyl-2- (4-trifluoromethoxybenzoylamino) ethyl] -2H-benzotriazol-4-ylmethyl} carbamic acid (100 mg) in DCM (2 ml) trimethylsilyl iodide (0.05 ml) was added. After 20 minutes, the mixture was quenched with methanol and concentrated under reduced pressure. The residue was taken up in ethyl acetate, washed with saturated sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the title compound as a white solid (70 mg, 87%). KG = 0.2 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 453. Ή NMR: (500 MHz, chloroform-ά): 1.86 (s, 3H), 4.21 (d, 1 = 3.4 Hz, 2H), 5.16 (d, 1 = 13.7 Hz, 1H), 5.43 (d, 1 = 13.8 Hz, 1H), 7.30 (d, 1 = 8.4 Hz, 2H), 7.33 (d, 1 = 0.7 Hz, 1H) 7.60 (s, 1H), 7.75 (d, 1 = 1.5 Hz, 1H) and 7.88 (d, 1 = 8.7 Hz, 2H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -57.1 (s, 3P).

Starting material {6-chloro-2- [2-cyano-2-methyl-2- (4-trifluoromethoxybenzoylamino) ethyl] -2H-benzotriazol-4-ylmethyl} carbamic acid tert-butyl ester [0.25 g, 60% , MS (ES): M / Ζ [M + H] = 553)] is obtained using a procedure similar to that described in Example 1, except for the use of tert-butyl ether [2- (2-amino-2- cyano-2methylethyl) -6-chloro-2H-benzotriazol-4-ylmethyl] carbamic acid (0.28 g), which was obtained using a procedure similar to that described in example 1, part b, except for use as the starting material [6-chloro-2- (2-oxopropyl) -2H-benzotriazole-4ylmethyl] carbamic acid tert-butyl ester (0.4 g), which was prepared as follows.

a. 1- (4-Bromo-6-chloro-2H-benzotriazol-2-yl) propan-2-one (3.5 g), zinc cyanide (2.8 g), zinc powder (0.4 g) and bis - (tri-tert-butylphosphine) palladium (0.62 g) is heated in degassed dimethylacetamide (60 ml) at 60 ° C. After stirring for 2 hours, the mixture was diluted with water. The resulting solid residue is filtered off, washed with water and transferred to ethyl acetate. The organic layer was filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 6-chloro-2- (2-oxopropyl) -2H-benzotriazole-4-carbonitrile as a white solid ( 2 g, 70%). KG = 0.55 (1: 1 EA / heptane). 1- (4-Bromo-6-chloro-2H-benzotriazole-2yl) propan-2-one is obtained using a procedure similar to that described in example 1, part a, except for using 7-bromo-5-chlorine as the starting material -1H-benzotriazole described in example 38, part a and b.

b. To a solution of 6-chloro-2- (2-oxopropyl) -2H-benzotriazole-4-carbonitrile in methanol (160 ml) at 0 ° C, di-tert-butyl carbonate (7.6 g) and nickel chloride hexahydrate (0, 4 g), followed by slow addition over 1.5 hours of sodium borohydride (5.2 g). After stirring for another 1 h, the mixture was treated with diethylene triamine (1.8 ml), concentrated under reduced pressure, transferred to ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give a brown residue (5.6 g) that contained tert-butyl ether [6-chloro-2- (2-hydroxypropyl) -2H

- 47 016912 benzotriazol-4-ylmethyl] carbamic acid and the dehalogen analogue of the [2- (2hydroxypropyl) -2H-benzotriazol-4-ylmethyl] carbamic acid tert-butyl ester. This residue is directly used in the third stage without further purification.

from. To a solution of oxalyl chloride (0.8 ml) in DCM (20 ml), a solution of DMSO (1.2 ml) in DCM (10 ml) was added dropwise at −78 ° C. under a nitrogen atmosphere. After stirring for 10 minutes, a solution of the crude residue containing 6-chloro- [2- (2-hydroxypropyl) -2H-benzotriazole-4ylmethyl] carbamic acid tert-butyl ester (1.45 g) in DCM (5 ml) was added drop by drop under nitrogen. After stirring for 30 minutes, TEA (5 ml) was added under nitrogen and the mixture was allowed to warm to room temperature. The mixture was concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain [6-chloro-2- (2oxopropyl) -2H-benzotriazol-4-ylmethyl] carbamic acid tert-butyl ester as yellow solid (0.4 g, 30%). B £ = 0.45 (1: 1 EA / heptane). Ή NMR: (400 MHz, chloroform-b): 1.41 (s, 9H), 2.19 (s, 3H), 4.71 (d, 1 = 5.3 Hz, 2H), 5.21 ( broad s, 1H), 5.50 (s, 2H), 7.30 (d, 1 = 0.8 Hz, 1H) and 7.78 (d, 1 = 1.3 Hz, 1H).

The compounds of examples 69-74 obtained according to the following General reaction scheme:

Rt! = SR _3, R ₉ = C1, R = OSG ₃ og SGI ₃ R? = C1, R ₉ = CE ₃ K = EFE ₃ og 8SE ₃ Cp = Br, R ₉ = C (K = SRF ₃ og ZSE ₃ Kn = Br, = C1, K = OCP ₃ og ZSR ₃

4-SE ₃ PH (B (OH) ₂

Cp CAT Pc1 - SR _3, Kd = CN, R ₃ = EFE og 5SR ₃

Κ-ι 1 ⁼ SI, P9 С SG3, K ⁼ OCP3 30 P3 Κ _{11 =} ΟΝ, K ₉ = C1, K = OCP ₃ K _n = 4-CP ₃ Pb, Kd = 01, P = OCP ₃ sa ( . - cat. Og - or

Final product:

At CH; A SV ,; X = CH; Υ ^^;

Ο = Γ = Ν;

B ₃ B ₄ N; a = 1; B ₅ = CH ₃ ; B ₆ = H;

2 = C (O); B ₇ = p-phenyl-B.

Example 69. No. [1-Cyano-2- (4-cyano-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.054).

No. [2- (4-Chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (100 mg described in Example 19), zinc cyanide (50 mg) , zinc powder (10 mg), 2-di-tert-butylphosphino-1,1'-binaphthyl (40 mg) and palladium trifluoroacetate (34 mg) are heated under nitrogen in degassed dimethylacetamide (1 ml) at 100 ° C. overnight. The mixture was concentrated under reduced pressure to give a residue, which was purified by chromatography (81O ₂ , heptane / EA) to give the title compound as a white solid (62 mg, 63%). B £ = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 483. NMR: (400 MHz, DMSO-b ₆ ): 1.77 (s, 3H), 5.56 (d, 1 = 13.3 Hz, 1H), 5.66 (d, 1 = 13.3 Hz,

1H), 7.49 (d, 1 = 8.2 Hz, 2H), 7.92 (d, 1 = 8.6 Hz, 2H), 8.59 (s, 1H), 8.90 (s, 1H) and 9.02 (s, 1H). ¹⁹ P NMR (376

MHz, DMSO-b ₆ ): -61.0 (s, 3P) and -57.1 (s, 3P).

Example 70. No. [1-Cyano-2- (4-cyano-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-methylethyl] -4 trifluoromethylthiobenzamide (compound No. 1.055).

Using a procedure similar to that described in Example 69, except for using No. [2- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (100 mg described in Example 20), the title compound was isolated as a white solid (52 mg, 53%). B £ = 0.5 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 499. NMR: (400 MHz, DMSO-b ₆ ): 1.77 (s, 3H), 5.57 (d, 1 = 13.2 Hz, 1H), 5.67 (d, 1 = 13.3 Hz, 1H), 7.84 (d, 1 = 8.3 Hz, 2H), 7.90 (d, 1 = 8.4 Hz, 2H), 8.60 (d, 1 = 1.1 Hz, 1H) 8.99 (s, 1H) and 9.01 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.0 (s, 3P) and -61.0 (s, 3P).

Example 71. N- [1-Cyano-2- (6-cyano-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.056).

Using a procedure similar to that described in Example 69, except for using No. [2- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (100 mg described in Example 32), the title compound was isolated as a white solid (44 mg, 45%). B £ = 0.55 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 483. NMR: (400 MHz, DMSO-b ₆ ): 1.78 (s, 3H),

5.53 (d, 1 = 13.2 Hz, 1H), 5.68 (d, 1 = 13.3 Hz, 1H), 7.48 (d, 1 = 8.1 Hz, 2H), 7, 89 (d, 1 = 8.8 Hz, 2H), 8.32 (s, 1H), 8.85 (s, 1H) and 9.18 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -61.7 (s, 3P) and -57.2 (s, 3P).

Example 72. N- [1-Cyano-2- (6-cyano-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.066).

Using a procedure similar to that described in Example 69, except for using Ν- [2 (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (590 mg described in Example 33), the title compound was isolated as a white solid (320 mg, 55%). B £ = 0.5 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 499. NMR: (400 MHz, DMSO-b ₆ ): 1.78 (s, 3H), 5.53 (d, 1 = 13.2 Hz, 1H), 5.69 (d, 1 = 13.3 Hz, 1H), 7.79-7.91 (m, 4H), 8.31 (s, 1H), 8.94 (s, 1H) and 9.18 (s, 1H). ¹⁹ P NMR

- 48 016912 (376 MHz, DMSO- ₆ ): -42.1 (s, 3P) and -61.7 (s, 3P).

Example 73. No. [2- (6-Chloro-4-cyano-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.067).

Using a procedure similar to that described in Example 69, except for using No. [2- (4-bromo-6-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (100 mg ) described in Example 38 and bis- (tri-tert-butylphosphine) palladium (20 mg) as a palladium catalyst containing no additional phosphine ligand and heating the reaction mixture at 60 ° C. for 1 h; the title compound is isolated as a white solid (70 mg, 79%). Κί = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 449. NMR: (400 MHz, dichloromethane ₂ ): 1.87 (s, 3Η), 5.28 (d, 1 = 13.7 Hz, 1Η), 5.52 (d, 1 = 13.7 Hz, 1Η), 7.29-7.43 (m, 3Η), 7.85 (d, 1 = 1.8 Hz, 1H), 7.87-7.95 (m, 2H) and 8.20 (d , 1 = 1.7 Hz, 1H). ¹⁹ P NMR (376 MHz, dichloromethane ₂ ): -58.5 (s, 3P).

Example 74. No. 2- [6-Chloro-4 - ((4-trifluoromethylphenyl) -2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 1.068).

No. [2- (4-Bromo-6-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (120 mg) described in example 38, bis- (three-tert β-butylphosphine) palladium (20 mg), bis (dibenzylideneacetone) palladium (20 mg), potassium fluoride (42 mg) and 4-trifluoromethylphenylboronic acid (45 mg) in THF are stirred at room temperature for 3 days. The mixture was concentrated under reduced pressure to obtain a residue, which was purified by chromatography (δίΟ ₂ , heptane / EA) to obtain a 1: 1 mixture of the title compound and the starting material [110 mg, Κί = 0.3 (3: 7 EA / heptane) ]. This mixture was further purified by preparative liquid chromatography (methanol / water) to obtain the title compound as a pure solid (35 mg, 26%). MS (ES): M / Ζ [M + H] = 568. NMR: (400 MHz, DMSO _6th ): 1.74 (s, 3Η), 1.84 (s, 1H), 5.39 (d, 1 = 13.3 Hz, 1Η), 5.64 ( d, 1 = 13.3 Hz, 1H), 7.41 (d, 1 = 8.0 Hz, 2 N), 7.60 (d, 1 = 8.3 Hz, 2H), 7.84 (d , 1 = 1.8 Hz, 1Η), 7.93 (d, 1 = 8.9 Hz, 2H), 8.12 (d, 1 = 8.1 Hz, 2 N) and 8.23 (d, 1 = 1.8 Hz, 1H). ¹⁹ P NMR (376 MHz, DMSO- ₆ ): -61.8 (s, 3P) and -57.3 (s, 3P).

The compounds of examples 75-84 receive according to the following General reaction scheme:

Final product:

ν ^ -Βρ A C-1A; X = C-I1ο; Υ = € -Κ _π ;

O = P = No.

Κ ₃ = Κ. · Ι = Η; a = 1; And, = CH ₃ ; Κ ... Η;

Ζ = ί '(Ο); I- = p-phenyl-I; And = 8 (O) _p CP ₃ ; n = 0, 1 or 2.

Example 75. Ν- [1-Cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylsulfinylbenzamide (compound No. 1.022).

3-Chloroperbenzoic acid (77% pure, 0.13 g) was added at 0 ° C to a solution of No. [1-cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide ( 0.11 g described in Example 22) in DCM. The reaction mixture was stirred for 72 hours at room temperature. The reaction mixture was diluted with DCM, then washed with saturated sodium bicarbonate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue which was purified by chromatography (8ίΟ _2, heptane / EA) to give the title compound as white solids (60 mg, 53%). MS (ES): M / Ζ [M + H] = 447. ¹ H NMR: (400 MHz, DMSO-6): 1.77 (s, 3Η), 5.4-5.65 (m, 2H), 7.76 (d, 1 = 8.8 Hz, 1Η) 8.02-8.07 (m, 4H), 7.94 (d, 1 = 8.9 Hz, 1Η), 8.78 (s, 1Η) and 9.10 (s, 1Η). ¹⁹ P NMR (376 MHz, DMSO-6): -74.20 (s, 3P).

Example 76. Ν- [2 - (4-Chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) - 1-cyano -1-methylethyl] -4 trifluoromethylsulfinyl benzamide (compound No. 1.023).

Using a procedure similar to that described in Example 75, except for using the Ν- [1-cyano-1-methyl-2- (4-chloro-6-trifluoromethylbenzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide described in Example 20 , the title compound is isolated as a white solid (60 mg, 53%). MS (ES): M / Ζ [M + H] = 524. ¹ H NMR: (400 MHz, DMSO-6): 1.78 (s, 3Η), 5.46-5.56 (m, 2H), 7.94 (d, 1Η, 1 = 0.7 Hz) 8.01-8.07 (m, 4H), 8.56 (d, 1 = 0.8 Hz, 1Η) and 9.02 (s, 1Η). ¹⁹ P NMR (376 MHz, DMSO-6): -74.27 (s, 3P) and -61.08 (s, 3P).

Example 77. Ν- [1-Cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylsulfinylbenzamide (compound No. 1.024).

3-Chloroperbenzoic acid (77% pure, 0.57 g) was added at 0 ° C to a solution of No. [1-cyano-2 (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4 trifluoromethylthiobenzamide (0.3 g described in Example 16) in DCM. The reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with DCM, washed with saturated aqueous sodium bicarbonate. The organic phase is dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which is purified by chromatography (δίΟ ₂ , heptane / EA) to obtain

- 49 016912 title compound as a white solid (100 mg, 32%). KG = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 490. NMR: (400 MHz, DMSO-b ₆ ): 1.76 (s, 3H), 5.39-5.60 (m, 2H), 7.74 (d, 1 = 1.6 Hz, 1H), 7.998.08 (m, 4H), 8.18 (dd, 1 = 1.5, 0.9 Hz, 1H), and 9.04 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -74.24 (s, 3P).

Example 78. Ν- [1-Cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.025).

The crude residue described in the experimental part of Example 77, which is purified by chromatography (81O ₂ , heptane / EA), also contains a sulfone corresponding to the title compound as a white solid (100 mg, 31%). KG = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 506. NMR: (400 MHz, DMSO-b ₆ ): 1.76 (s, 3H), 5.51 (dd, 1 = 60.1, 13.4 Hz, 1H), 7.73 (d, 1 = 1 6 Hz, 1H), 8.12-8.17 (m, 2H), 8.19 (d, 1 = 1.6 Hz, 1H), 8.31 (d, 1 = 8.4 Hz, 2H ) and 9.19 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -78.70 (s, 3P).

Example 79. No. [1-Cyano-1-methyl-2- (5-trifluoromethyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.026).

3-Chloroperbenzoic acid (60 mg) was added at 0 ° C to a solution of No. [1-cyano-1-methyl-2- (5 trifluoromethyl-2H-benzotriazol-2-yl-1) ethyl] -4-trifluoromethylthiobenzamide (50 mg, described in example 11) in DXM. The reaction mixture was stirred for 48 hours at room temperature, then 3-chloroperbenzoic acid (60 mg) was added and the reaction mixture was stirred for 48 hours at room temperature. The reaction mixture was diluted with DCM, washed with saturated aqueous sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a residue, which was purified by chromatography (81O ₂ , heptane / EA) to give the title compound as a white solid (42 mg, 79%). 1 (= 0.5 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 506. ^! H NMR: (400 MHz, chloroform-b): 1.90 (s, 3H), 5.40 (dd, 1 = 120.3, 13.8 Hz, 2H), 7.38 (br s, 1H), 7.66 (dd, 1 = 9.1, 1.5 Hz, 1H), 8.07-8.14 (m, 2H), 8.16-8.23 (m, 2H) and 8.26 (br s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b) : -78.33 (s, 3P) and

-63.04 (s, 3P).

Example 80. Ν- [1-Cyano-1-methyl-2- (5-cyano-2H-benzotriazol-2-yl) -1-ethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.027).

Using a procedure similar to that described in Example 79, except for using No. [1-cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (50 mg described in the example 22), the title compound is isolated as a white solid (35 mg, 65%). KG = 0.4 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 463. ^! H NMR: (400 MHz, DMSO-b6): 1.76 (s, 3H), 5.44-5.65 (m, 2H), 7.77 (d, 1 = 8.8 Hz, 1H), 8.15 (d, 1 = 8.6 Hz, 2H), 8.19 (d, 1 = 8.8 Hz, 1H), 8.32 (d, 1 = 8.4 Hz, 2H), 8, 79 (s, 1H) and 9.26 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -78.67 (s, 3P).

Example 81. No. [2- (4-Chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethylsulfonylbenzamide (compound No. 1.028).

Using a procedure similar to that described in Example 77, except for using No. [2- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (50 mg described in Example 20) and a 6-fold excess of 3-chloroperbenzoic acid (77% pure, 130 mg), the title compound was isolated as a white solid (35 mg, 66%). KG = 0.65 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 540. ^! H NMR: (400 MHz, DMSO-b6): 1.78 (s, 3H), 5.59 (dd, 1 = 58.3, 13.3 Hz, 2H), 7.93 (s, 1H), 8.16 (d, 1 = 8.58 Hz, 2H), 8.57 (s, 1H) and 9.17 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -78.73 (s, 3P) and -61.08 (s, 3P).

Example 82. No. [2- (2H-Benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.029).

Sodium periodate (200 mg) and ruthenium chloride (10 mg) were added to a solution of No. [2- (2H-benzotriazole-2yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (100 mg described in example 6), in a mixture of acetonitrile-water (2: 1). The reaction mixture was stirred for 48 hours, after which the mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic filtrate was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a residue, which was purified by chromatography (81O ₂ , heptane / EA) to give the title compound as a white solid (50 mg, 46%). KG = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 438. ^! H NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.39-5.53 (m, 2H), 7.47 (dd, 1 = 6.6, 3.1 Hz, 2H), 7.95 (dd, 1 = 6.6, 3.1 Hz, 2H), 8.17 (d, 1 = 8.6 Hz, 2H), 8.31 (d, 1 = 8 4 Hz, 2H) and 9.25 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -78.66 (s, 3P).

Example 83. No. [1-Cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.030).

Using a procedure similar to that described in Example 77, except for using No. [1-cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (50 mg described in Example 8), the title compound was isolated as a white solid (40 mg, 37%). KG = 0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 452. ^! H NMR: (400 MHz, DMSO-b6): 1.73 (s, 3H), 5.34-5.47 (m, 2H), 7.30 (dd, 1 = 8.8, 1.4 Hz) , 1H), 7.69 (s, 1H), 7.83 (d, 1 = 8.8 Hz, 1H), 8.17 (d, 1 = 8.5 Hz, 2H), 8.32 (d , 1 = 8.4 Hz, 2H) and 9.24 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -78.67 (s, 3P).

- 50 016912

Example 84. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.031).

Using a procedure similar to that described in Example 79, except for using No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (50 mg described in the example 3), the title compound is isolated as a white solid (120 mg, 45%). Κί'0.6 (1: 1 EA / heptane). MS (ES): M / Ζ [M + H] = 472. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 5.41-5.52 (m, 2H), 7.49 (m, 1H), 8.02 (m, 1H), 8.14-8.32 (m, 4H) and 9.25 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -78.67 (s, 3E).

The compounds of examples 85-88 receive according to the following General reaction scheme:

Final product:

ν ^ -H; A = C-C1; X = CH; Υ ^ -H;

Ο = Ρ = Ν;

K ₃ = K ₄ = H; a = 1; Ke = H;

Ζ = Ο (Θ); K ₇ = p-phenyl-K; K = ₃ or EFE 8SE _3.

Example 85. Ν- {1 - [(5-Chloro-2H-benzotriazol-2-yl) methyl] -1-cyanopropyl} -4-trifluoromethoxybenzamide (compound No. 1.047).

Using a procedure similar to that described in Example 79, except for the use of 2-amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] butyronitrile, the title compound was isolated as a white solid. MS (ES): M / Ζ [M + H] = 438. ¹ H NMR: (400 MHz, chloroform-b): 1.29 (t, 1 = 7.4 Hz, 3H), 1.72-1.94 (m, 1 = 14.4, 7.4 Hz, 1H), 2.29 (m, 1 = 14.3, 7.4 Hz, 1H), 5.23 (d, 1 = 13.9 Hz, 1H), 5.47 (d, 1 = 13.8 Hz, 1H), 7.15 (s, 1H), 7.33 (d, 1 = 8.2 Hz, 2H), 7.40 (dd, 1 = 9.1, 1.8 Hz, 1H), 7.82 (d, 1 = 9.1 Hz, 1H), 7.85 (d, 1 = 8.7 Hz, 2H) and 7.87 (d, 1 = 1.2 Hz, 1H). ¹⁹ E NMR (376 MHz, chloroform-b): -58.1 (s 3E).

2-amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] butyronitrile was obtained using the procedure similar to that described in example 1, part b, except for using 1- (5-chlorine as the starting material). -2H-benzotriazol-2-yl) butan-2-one, which is prepared as follows.

a. A solution of 5-chloro-2H-benzotriazole (1.53 g) in THF is added at 0 ° C. to a mixture of azisicarboxylic acid diisopropyl ester (2 ml), triphenylphosphine (2.9 g) and allyl alcohol (1.4 ml) in THF . After stirring for 1 h, the mixture was concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 2-allyl-5-chloro-2H-benzotriazole (1.02 g, 53%). A mixture of 1-allyl-5-chloro-1H-benzotriazole and 1-allyl-6-chloro-1H-benzotriazole is also regenerated (0.9 g, 47%). Alternatively, 2-allyl-5-chloro-2H-benzotriazole [4.87 g, 25%, Κί = 0.4 (1: 3 EA / heptane)] is obtained using a procedure similar to that described in example 1, part a , except for the use of 3-bromopropene. Similarly, a mixture of 1-allyl-5-chloro-1H-benzotriazole and 1-allyl-6-chloro-1H-benzotriazole also regenerates [10.81 g, 56%, Κί = 0.2 (1: 3 EA / heptane) ].

b. 2-Allyl-5-chloro-2H-benzotriazole, dissolved in a mixture of DCM and methanol, is treated with gaseous ozone for 30 minutes. After stirring for 1 h at -78 ° C, the mixture was purged with oxygen for 10 min and then quenched with dimethyl sulfide, followed by treatment with 10% sodium thiosulfate solution and diluted with DCM (100 ml). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to quantitate 2- (5-chloro-2H-benzotriazol-2-yl) -1-methoxyethanol.

c. To a solution of 2- (5-chloro-2H-benzotriazol-2-yl) -1-methoxyethanol (300 mg) in THF was added a 2 M solution of ethyl magnesium bromide, Grignard reagent (1.6 ml) at -78 ° C in a nitrogen atmosphere, and the mixture was allowed to slowly warm to room temperature. The mixture was quenched with a saturated solution of ammonium chloride, and then magnesium sulfate. The solids formed are filtered off and the organic layer is concentrated under reduced pressure to obtain a residue, which is purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (5-chloro-2H-benzotriazol-2-yl) butan-2-ol (107 mg). Κί = 0.7 (2: 1 EA / heptane).

b. 1- (5-Chloro-2H-benzotriazol-2-yl) butan-2-ol in DCM interacts with the Dessa Martina Ayeg periodinan. After stirring at room temperature, the mixture was concentrated under reduced pressure and purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (5-chloro-2H-benzotriazole-51 016912

2-yl) butan-2-one.

Example 86. Ν- {1 - [(5-Chloro-2H-benzotriazol-2-yl) methyl] -1-cyanopropyl} -4-trifluoromethylthiobenzamide (compound No. 1.048).

Using a procedure similar to that described in Example 1, except for the use of 2amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] butyronitrile described in Example 85 and 4 trifluoromethylbenzoyl chloride, the title compound was isolated as a white solid . MS (ES): M / Ζ [M + H] = 454. ^! H NMR: (400 MHz, chloroform-b): 1.29 (t, 1 = 7.4 Hz, 3H), 1.77-1.94 (m, 1 = 14.4, 7.4, 7, 4, 7.3 Hz, 1H), 2.16-2.36 (m, 1 = 14.4, 7.4, 7.4, 7.3 Hz, 1H), 5.23 (d, 1 = 13.9 Hz, 1H), 5.47 (d, 1 = 13.8 Hz, 1H),

7.21 (s, 1H), 7.39 (dd, 1 = 9.1, 1.9 Hz, 1H), 7.73-7.79 (m, 2H), 7.79-7.85 ( m, 3H) and 7.87 (dd, 1 = 1.8, 0.7 Hz, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -42.3 (s, 3P).

Example 87. Ν- {1 - [(5-Chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-3-methylbutyl} -4-trifluoromethoxybenzamide (compound No. 1.049).

Using a procedure similar to that described in Example 1, except for the use of 2amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -4-methylpentanonitrile, the title compound was isolated as a solid. MS (ES): M / Ζ [M + H] = 466. ¹ H NMR: (400 MHz, chloroform-b): 1.11 (d, 1 = 6.4 Hz, 3H), 1.14 (d, 1 = 6.3 Hz, 3H), 1.79-1 90 (m, 1H), 2.05-2.21 (m, 2H), 5.27 (d, 1 = 13.8 Hz, 1H), 5.48 (d, 1 = 13.8 Hz, 1H), 7.27 (s, 1H), 7.32 (d, 1 = 8.5 Hz, 2H), 7.39 (dd, 1 = 9.1, 1.7 Hz, 1H), 7, 78-7.86 (m, 3H) and 7.87 (d, 1 = 1.8 Hz, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -4-methylpentanonitrile was obtained using the procedure similar to that described in example 1, part b, except for using 1- ( 5-chloro-2H-benzotriazol-2-yl) -4-methylpentan-2-one. 1- (5-Chloro-2H-benzotriazol2-yl) -4-methylpentan-2-one is obtained using a procedure similar to that described in Example 85, part a-b, except for the use of isopropyl magnesium bromide as Grignard reagent in part c.

Example 88. Ν- {1 - [(5-Chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-3-methylbutyl} -4-trifluoromethylthiobenzamide (compound No. 1.050).

Using a procedure similar to that described in example 1, except for the use of 2 amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -4-methylpentanonitrile described in example 87 and 4 trifluoromethylbenzoyl chloride, the title compound was isolated in as a solid. ¹ H NMR: (400 MHz, chloroform-b): 1.11 (d, 1 = 6.5 Hz, 3H), 1.15 (d, 1 = 6.4 Hz, 3H), 1.78-1 91 (m, 1H), 2.06-2.21 (m, 2H), 5.27 (d, 1 = 13.8 Hz, 1H), 5.49 (d, 1 = 13.8 Hz, 1H), 7.16 (s, 1H), 7.40 (dd, 1 = 9.1, 1.8 Hz, 1H), 7.75-7.80 (m, 2H), 7.807.86 (m , 3H) and 7.87 (dd, 1 = 1.8, 0.5 Hz, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -42.2 (s, 3P).

The compounds of examples 89 and 90 are prepared according to the following general reaction scheme:

Final product:

ν ^ -4; No. = C-C1; X = CH; Υ ^ -H;

Ο = ί = Ν;

B3 = B4 = H; a = 1; B5 = tert-butyl; B6 = H;

Ζ = Ο (Ό); B ₇ = p-phenyl-B.

Example 89. Ν- {1 - [(5-Chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-2,2-dimethylpropyl} -4-trifluoromethoxybenzamide (compound No. 1.051).

Using a procedure similar to that described in Example 1, with the exception of using 2amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -3,3-dimethylbutyronitrile, a bisamide derivative, Ν- {1- [ (5-chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-2,2-dimethylpropyl} -4-trifluoromethoxy-Y- (4-trifluoromethoxybenzoyl) benzamide instead of the title compound. MS (ES): M / Ζ [M + H] = 654. Subsequent treatment with lithium hydroxide in methanol and purification by chromatography (81O ₂ , heptane / EA) leads to the title compound as a solid. MS (ES): M / Ζ [M + H] = 466. ¹ H NMR: (400 MHz, chloroform-b): 5.17 (s, 9H), 5.34 (d, 1 = 14.1 Hz, 1H), 5.51 (d, 1 = 14.1 Hz , 1H), 7.02 (s, 1H), 7.35 (d, 1 = 8.0 Hz, 2H), 7.38 (dd, 1 = 9.1, 1.9 Hz, 1H), 7 79 (dd, 1 = 9.1, 0.6 Hz, 1H), 7.84 (dd, 1 = 1.8, 0.6 Hz, 1H) and 7.89 (d, 1 = 8.8 Hz, 2H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

- 52 016912

2-amino-2- [5-chloro-2H-benzotriazol-2-yl) methyl] -3,3-dimethylbutyronitrile was obtained using the procedure similar to that described in example 1, parts a and b, except for using 1-chloro, 3-dimethylbutan-2-one instead of chloroacetone in part a.

Example 90. Ν- {1 - [(5-Chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-2,2-dimethylpropyl} -4-trifluoromethylthiobenzamide (compound No. 1.052).

Using a procedure similar to that described in Example 1, except for using 2amino-2 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -3,3-dimethylbutyronitrile described in Example 89, and

4-trifluoromethylbenzoyl chloride, a bis-amide derivative was isolated, No. {1 - [(5-chloro-2H-benzotriazol2-yl) methyl] -1-cyano-2,2-dimethylpropyl} -4-trifluoromethylthio-Y- (4-trifluoromethylthiobenzoyl ) benzamide instead of the title compound. MS (ES): M / Ζ [M + H] = 686. Subsequent treatment with lithium hydroxide in methanol and purification by chromatography (81O ₂ , heptane / EA) leads to the title compound as a solid. MS (ES): M / Ζ [M + H] = 482. Ή NMR: (400 MHz, chloroform-6): 1.17 (s, 9H), 5.35 (d, 1 = 14.1 Hz, 1H), 5.51 (d, 1 = 14.1 Hz, 1H), 7.06 (s, 1H), 7.38 (dd, 1 = 9.1, 1.9 Hz, 1H), 7.75-7.82 (m, 3H), 7.84 (dd , 1 = 1.8, 0.6 Hz, 1H) and 7.85-7.91 (m, 2H). ¹⁹ P NMR (376 MHz, chloroform-6): -42.3 (s, 3P).

The compounds of examples 90 and 92 are prepared according to the following general reaction scheme:

Final product:

ν ^ -4; W = C-C1; X = CH; Υ ^ -H;

Ο = ί = Ν;

B ₃ N; a = 1; B ₅ = CH ₂ OH; B ₆ = H;

Ζ = Ο (Θ); B ₇ = p-phenyl-B.

Example 91. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1- (hydroxymethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.058).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-2 - [(5-chloro-2H-benzotriazol-2-yl) -2- (hydroxymethyl) propionitrile, an ester derivative, 2-amino-3- was isolated [(5-chloro-2H-benzotriazol-2-yl) -2-cyanopropyl ester of 4 trifluoromethoxybenzoic acid instead of the title compound. This ether is reacted with an additional amount of 4-trifluoromethoxybenzoyl chloride, then treated with lithium hydroxide in methanol and purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound as a solid. MS (ES): M / Ζ [M + H] = 440. ¹ H NMR: (400 MHz, chloroform-6): 3.27 (t, 1 = 7.3 Hz, 1H), 3.94 (dd, 1 = 11.9, 7.3 Hz, 1H), 4 30 (dd, 1 = 11.9, 5.9 Hz, 1H), 5.43 (d, 1 = 13.9 Hz, 1H), 5.48 (d, 1 = 14.0 Hz, 1H) 7.33 (d, 1 = 8.1 Hz, 2H), 7.43 (dd, 1 = 9.1, 1.9 Hz, 1H), 7.45 (s, 1H), 7.82- 7.89 (m, 3H) and 7.90 (dd, 1 = 1.8, 0.6 Hz, 1H). ¹⁹ P NMR (376 MHz, chloroform-6): -58.1 (s, 3P).

2-amino-3 - [(5-chloro-2H-benzotriazol-2-yl) -2- (hydroxymethyl) propionitrile was obtained using the procedure similar to that described in example 1, part b, except for using 1- as the starting material (tert-butyldimethylsilyloxy) -3- (5-chloro-2H-benzotriazol-2-yl) propan-2-one, which is obtained as follows (tert-butyldimethylsilyl protecting group is removed under the Strecker reaction conditions).

a. To a solution of 2-allyl-5-chloro-2H-benzotriazole (5.2 g) described in Example 85, part a, in a mixture (10: 1) of THF and water (45 ml), 50% solution of 4-methylmorpholine S-oxide in water (7 ml) and then 4% solution of osmium tetroxide in water (2 ml). After stirring at room temperature, the mixture was quenched with 10% sodium thiosulfate solution, extracted with ethyl acetate and concentrated under reduced pressure. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain 3- (5-chloro-2 # benzotriazol-2-yl) propan-1,2-diol (4.8 g, 79%), which was used directly in the next step without further purification.

b. To a solution of 3- (5-chloro-2H-benzotriazol-2-yl) propan-1,2-diol (1.09 g) in DCM at 0 ° C are added imidazole (0.65 g) and tert-butyldimethylsilyl chloride (0 , 8 g). After stirring overnight at room temperature, the mixture was diluted with DCM, washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (tert-butyldimethylsilyloxy) -3- (5-chloro-2H-benzotriazole-2yl) propan-2-ol (1.5 g, 85%). HB = 0.55 (1: 1 EA / heptane).

1- (tert-Butyldimethylsilyloxy) -3- (5-chloro-2H-benzotriazol-2-yl) propan-2-ol (1.5 g) in DCM (20

- 53 016912 ml) interacts with the Dess-Martin periodinan (2.1 g).

After stirring overnight at room temperature, the mixture was concentrated under reduced pressure and purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (tert-butyldimethylsilyloxy) -3- (5-chloro-2H-benzotriazol-2-yl) propan-2 -one (1.2 g).

Example 92. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1- (hydroxymethyl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.059).

When using a procedure similar to that described in example 1, except for the use of 2amino-2 - [(5-chloro-2H-benzotriazol-2-yl) -2- (hydroxymethyl) propionitrile described in example 91, and 4-trifluoromethylbenzoyl chloride were the ester derivative, 2-amino-3 - [(5-chloro-2H-benzotriazol-2-yl) -2-cyanopropyl ester of 4-trifluoromethylbenzoic acid, was isolated instead of the title compound. This ether is reacted with an additional amount of 4 trifluoromethylbenzoyl chloride, then the mixture is treated with lithium hydroxide in methanol and purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound as a solid. MS (ES): M / Ζ [M + H] = 456. ¹ H NMR: (400 MHz, chloroform-b): 3.31 (br s, 1H), 3.94 (d, 1 = 11.8 Hz, 1H), 4.31 (d, 1 = 11.7 Hz, 1H), 5.43 (d, 1 = 14.0 Hz, 1H), 5.49 (d, 1 = 13.9 Hz, 1H), 7.43 (dd, 1 = 9.1, 1 , 9 Hz, 1H), 7.51 (s, 1H), 7.78 (d, 1 = 8.3 Hz, 2H), 7.84-7.87 (m, 3H) and 7.90 (dd , 1 = 1.8, 0.6 Hz, 1H). ¹⁹ E NMR (376 MHz, chloroform-b): 42.2 (s, 3E).

The compounds of examples 93-95 receive according to the following General reaction scheme:

Final product:

V = CH; ^ = C-C1; X = CH; Y = CH;

Ο = Γ = Ν;

ID = H4 = H; a = 1; And ₅ = CH ₂ X'Me; And ₆ = H;

Ζ ^^); I ₇ = p-phenyl-I; K = ₃ or EFE 8SE _3.

Example 93. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1- (methylthiomethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.061).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3 - [(5-chloro-2H-benzotriazol-2-yl) -2- (methylthiomethyl) propionitrile, the title compound is isolated as a solid MS (ES): M / Ζ [M + H] = 470. ¹ H NMR: (400 MHz, chloroform-b): 2.41 (s, 3H), 3.07 (d, 1 = 14.7 Hz, 1H), 3.52 (d, 1 = 14.6 Hz , 1H), 5.47 (dd, 2H), 7.34 (d, 1 = 8.5 Hz, 2H), 7.41 (dd, 1 = 9.1, 1.8 Hz, 2H) and 7 79-7.94 (m, 5H). ¹⁹ E NMR (376 MHz, chloroform-b): -58.1 (s, 3E).

2-amino-3- (5-chloro-2H-benzotriazol-2-yl) -2- (methylthiomethyl) propionitrile was obtained using the procedure similar to that described in example 1, parts a and b, except for using as starting material 1 - (5-chloro-2H-benzotriazol-2-yl) -3- (methylthio) propan-2-one, which is prepared as follows.

a. To a solution of 2-allyl-5-chloro-2H-benzotriazole (5.0 g) described in Example 85, part a, in DCM (50 ml), meta-chloroperbenzoic acid (8.5 g, 55% purity) was added. . After stirring at room temperature for 24 hours, the mixture was filtered through a pad of basic alumina. The filtrate was concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to give 5-chloro-2-oxiranylmethyl-2H-benzotriazole (0.7 g). YAG = 0.55 (2: 1 EA / heptane).

b. Sodium thiomethoxide (307 mg) was added to a solution of 5-chloro-2-oxiranylmethyl-2H-benzotriazole (306 mg) in methanol (5 ml). After stirring at room temperature, the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain 1- (5-chloro-2H-benzotriazol-2-yl) -3 (methylthio) propan-2-ol, which was used directly in the next step oxidation.

c. 1- (5-Chloro-2H-benzotriazol-2-yl) -3- (methylthio) propan-2-ol in DCM (5 ml) reacts with Dess-Martin periodinan (720 mg). After stirring overnight at room temperature, the mixture was concentrated under reduced pressure and purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (5-chloro-2H-benzotriazol-2-yl) -3- (methylthio) propan-2 -one (149 mg, 40% after two stages).

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Example 94. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1 - (methoxymethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.062).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3 - [(5-chloro-2H-benzotriazol-2-yl) -2- (methoxymethyl) propionitrile, the title compound was isolated as a solid. MS (ES): M / Ζ [M + H] = 454. ¹ H NMR: (400 MHz, chloroform-b): 3.52 (s, 3H), 3.71 (d, 1 = 9.8 Hz, 1H), 4.12 (d, 1 = 9.7 Hz , 1H), 5.37-5.47 (m, 2H), 7.33 (d, 2H), 7.40 (dd, 1 = 9.1, 1.9 Hz, 1H), 7.48 ( s, 1H) and 7.81-7.90 (m, 4H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-3 - [(5-chloro-2H-benzotriazol-2-yl) -2- (methoxymethyl) propionitrile was obtained using the procedure similar to that described in example 1, part b, except for using 1- as the starting material [(5-chloro-2H-benzotriazol-2-yl) -3-methoxypropan-2-one. 1- (5-Chloro-2H-benzotriazol-2-yl) -3-methoxypropan-2-one is obtained using a procedure similar to that described in Example 93, part ac, except for using sodium methoxide in part b.

Example 95. No. [2- (5-Chloro-2H-benzotriazol-2-yl) -1-cyano-1 - (methanesulfonylmethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.063).

To a solution of No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1- (methylthiomethyl) ethyl] -4-trifluoromethoxybenzamide (36 mg) in a mixture of DCM and TFA, 3 drops of hydrogen peroxide ( 30 wt.% In water). After stirring overnight at room temperature, the mixture was concentrated under reduced pressure to obtain the title compound as a solid. MS (ES): M / Ζ [M + H] = 502. ^! H NMR: (400 MHz, DMSO-b6): 3.03 (s, 3H), 4.13 (d, 1 = 5.0 Hz, 1H), 4.20 (d, 1 = 5.1 Hz, 1H), 5.54 (s, 2H), 7.43 (dd, 1 = 9.1, 1.9 Hz, N), 7.50 (d, 1 = 8.7, 0.8 Hz, 2H ), 7.68 (s, 1H), 7.81-7.90 (m, 2H), 7.91-8.00 (m, 2H), 8.05 (dd, 1 = 1.9, 0 6 Hz, 1H) and 8.29 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

The compounds of examples 96-104 obtained according to the following General reaction scheme:

Final product:

Y = CK ₈ ; \\ 'S-N .; X = CK ₁₀ ; Y = CK ₁₁ ;

OS-K-; Ρ = Ν;

K ₃ = H4 = H; a = 1; K ₅ = CH ₃ ; I ₆ = H;

Ζ = ί '(Ο); K ₇ = p-phenyl-K.

Example 96. No. [1-Cyano-1-methyl-2- (5-nitro-2H-indazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 2.001).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3-methyl-3- (5-nitro-2H-indazol-2-yl) propionitrile (62 mg), the title compound was isolated as a white solid. (100 mg, 91%). MS (ES): M / Ζ [M + H] = 434. ¹ H NMR: (400 MHz, DMSO-b6): 1.72 (s, 3H), 5.21 (q, 1 = 13.7 Hz, 2H), 7.53 (d, 1 = 8.2 Hz) , 2H), 7.81 (d, 1 = 9.5 Hz, 1H), 7.97 (d, 1 = 8.8 Hz, 2H), 8.01 (dd, 1 = 2.2 Hz, 1H ), 8.82 (s, 1H), 8.94 (d, 1 = 2.0 Hz, 1H) and 8.99 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

2-amino-3-methyl-3- (5-nitro-2H-indazol-2-yl) propionitrile was obtained using the procedure similar to that described in example 1, parts a and b, except for using commercially available 5 as the starting material -nitro-1H-indazole (7 g), the half-molar equivalent of potassium carbonate (3.1 g), one equivalent of potassium iodide (9.2 g) and heating the mixture while boiling in acetone to isolate the desired 1- (5-nitro-2H -indazol-2-yl) propan-2-one (890 mg, 9.5%) along with 1- (5-nitro-2Nindazol-1-yl) propan-2-one in part a.

Example 97. N- [1-Cyano-1-methyl-2- (5-nitro-2H-indazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 2.002).

Using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (5-nitro-2H-indazol-2-yl) propionitrile (62 mg described in example 96) and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid (96 mg, 84%). MS (ES): M / Ζ [M + H] = 450. ^! H NMR: (400 MHz, DMSO-b6): 1.72 (s, 3H), 5.22 (q, 2H), 7.81 (d, 1 = 9.5 Hz, 1H), 7.86- 7.90 (m, 2H), 7.92-7.97 (m, 2H), 8.00-8.05 (m, 1H), 8.83 (s, 1H), 8.95 (d, 1 = 1.9 Hz, 1H) and 9.07 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -41.9 (s, 3P).

- 55 016912

Example 98. No. [1-Cyano-2- (5,7-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.003).

Using a procedure similar to that described in Example 1, with the exception of using 2amino-3- (5,7-dichloro-2H-indazol-2-yl) -2-methylpropionitrile (60 mg), the title compound was isolated as a white solid ( 80 mg, 78%). MS (ES): M / Ζ [M + H] = 457. ¹ H NMR: (400 MHz, DMSO-b6): 1.70 (s, 3H), 5.11 (d, 1H), 5.23 (d, 1H), 7.51 (d, 1 = 8, 3 Hz, 2H), 7.89 (d, 1 = 1.6 Hz, 1H), 7.97 (d, 1 = 8.8 Hz, 2H), 8.53 (s, 1H), 8.94 (d, 1 = 2.0 Hz, 1H) and 8.95 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b6): -57.1 (s, 3E).

2-amino-3- (5,7-dichloro-2H-indazol-2-yl) -2-methylpropionitrile was obtained using the procedure similar to that described in example 1, parts a and b, except for using as starting material 5, 7-dichloro-1H-indazole (3 g) and heating the mixture while boiling in acetone to isolate the desired 1- (5,7-dichloro-1H-indazol-2-yl) propan-2-one (1.7 g, 44 %) together with 1- (5,7-dichloro-1H-indazole 1-yl) propan-2-one (1.2 g, 30%) in part a.

5,7-Dichloro-1H-indazole is obtained, as described below, using the procedures described in the literature for the preparation of indazoles substituted in a six-membered ring, see, for example, Y.A. WaPksN, e! a1. 1. Hegosus1. Oh. 1984, 21, 1063 and R. 8c Nitapp e! A1., Vuoguds & Furniture 1 SNMMu Leyegk, 2001, 11, 1153.

a. To a suspension of 2,4-dichloro-6-methylaniline (5 g) in a mixture of hydrochloric acid (7.5 ml) and water (7.5 ml), a solution of sodium nitrite (2 g) is slowly added at 0 ° C in a minimum amount of water. After all solid starting materials have been consumed, forming a yellow mixture, a solution of sodium tetrafluoroborate (4.4 g) in water (10 ml) is added. After stirring for 45 minutes at 0 ° C, the resulting solids were filtered off, washed with chilled methanol, washed with diethyl ether and dried in vacuo to give 2,4-dichloro-6-methylbenzenediazonium tetrafluoroborate (5.7 g).

b. A mixture of 2,4-dichloro-6-methyl-benzene-diazonium tetrafluoroborate (5.5 g), 18-crown-6 (271 mg) and potassium acetate (4 g) was stirred in chloroform (60 ml) for 1.5 hours at room temperature . The resulting crude mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain 5,7-dichloro-1H-indazole as a pale brown solid (3 g).

Example 99. No. [1-Cyano-2- (5,7-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.005).

Using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (5,7-dichloro-2H-indazol-2-yl) propionitrile (60 mg, described in example 98), 4 trifluoromethylthiobenzoyl chloride, title the compound is isolated as a white solid (80 mg, 76%). MS (ES): M / Ζ [M + H] = 473. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.70 (s, 3H), 5.11 (d, 1H), 5.25 (d, 1H), 7.48 (s, 1H), 7 84-7.91 (m, 3H), 7.95 (d, 2H), 8.54 (s, 1H) and 9.03 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -42.0 (s, 3E).

Example 100. No. [1-Cyano-2- (5,7-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-phenoxybenzamide (compound No. 2.004).

Using a procedure similar to that described in Example 1, except for the use of 2amino-2-methyl-3- (5,7-dichloro-2H-indazol-2-yl) propionitrile (60 mg, described in Example 98) and 4 phenoxybenzoyl chloride, the title compound is isolated as a white solid (90 mg, 87%). MS (ES): M / Ζ [M + H] = 465. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.71 (s, 3H), 5.12 (d, 1H), 5.21 (d, 1H), 7.04-7.13 (m, 4H), 7.23 (t, 1 = 7.4 Hz, 1H), 7.41-7.51 (m, 3H), 7.85-7.92 (m, 3H), 8.52 (s , 1H) and 8.80 (s, 1H).

Example 101. Ν- | 2- (5-Chloro-7-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.006).

Using a procedure similar to that described in Example 1, with the exception of using 2 amino-3- (5-chloro-7-methyl-2H-indazol-2-yl) -2-methylpropionitrile (58 mg), the title compound was isolated as a white solid substances (73 mg, 72%). MS (ES): M / Ζ [M + H] = 437. ¹ H NMR: (400 MHz, DMSO-b6): 1.69 (s, 3H), 2.39 (s, 3H), 5.05 (d, 1H), 5.19 (d, 1 = 13, 7 Hz, 1H), 7.03 (s, 1H), 7.52 (d, 1 = 8.2 Hz, 2H), 7.65 (d, 1 = 0.8 Hz, 1H), 7.97 (d, 1 = 8.7 Hz, 2H), 8.36 (s, 1H) and 8.89 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b6): -57.1 (s, 3E).

2-amino-3- (5-chloro-7-methyl-2H-indazol-2-yl) -2-methylpropionitrile was obtained using the procedure similar to that described in example 1, parts a and b, except for using as starting material 5-chloro-7-methyl-1H-indazole (6.9 g) and heating the mixture by boiling in acetone for 1.5 days to obtain 1- (5-chloro-7-methyl-2H-indazol-2-yl) propan-2-one (1.9 g) in part a.

5-Chloro-7-methyl-1H-indazole was prepared using a procedure similar to that described in Example 98, part a, and with the exception of using 4-chloro-2,6-dimethylaniline (5 g) as the starting material.

Example 102. No. [2- (5-Chloro-7-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.007).

When using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (5-chloro-7-methyl-2H-indazol-2-yl) propionitrile (58 mg described in example 101) and

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4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (77 mg, 73%). MS (ES): M / Ζ [M + H] = 453. ¹ H NMR: (400 MHz, DMSO-b6): 1.69 (s, 3H), 2.38 (s, 3H), 5.05 (d, 1H), 5.21 (d, 1H), 7 03 (s, 1H), 7.66 (s, 1H), 7.87 (d, 2H), 7.94 (d, 2H), 8.37 (s, 1H) and 8.97 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -42.0 (s, 3P).

Example 103. Y- [1-Cyano-2- (5,7-dichloro-3-methyl-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.010).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (5,7-dichloro-3-methyl-2H-indazol-2-yl) -2-methylpropionitrile (40 mg), the title compound was isolated as white solid (60 mg, 90%). MS (ES): M / Ζ [M + H] = 471. ¹ H NMR: (400 MHz, DMSO-b6): 1.82 (s, 3H), 2.73 (s, 3H), 4.98 (d, 1H), 5.08 (d, 1 = 13, 7 Hz, 1H), 7.45 (dd, 1H), 7.52 (d, 2H), 7.91 (d, 1H), 8.00-8.04 (m, 2H) and 9.09 ( s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

2-amino-3- (5,7-dichloro-3-methyl-2H-indazol-2-yl) -2-methylpropionitrile was obtained using the procedure similar to that described in example 1, parts a and b, except for using 5, 7dichloro-3-methyl-1H-indazole (400 mg) and heating the mixture by boiling in acetone to isolate 1- (5,7dichloro-3-methyl-2H-indazol-2-yl) propan-2-one (140 mg) in parts a.

5,7-Dichloro-3-methyl-1H-indazole was prepared using a procedure similar to that described in Example 98, parts a and b, except for using 2,4-dichloro-6-ethylaniline (2.9 g) as the starting material, which is obtained by chlorination of 6-ethylaniline (10 g) with Ν-chlorosuccinimide (22 g) in acetonitrile (80 ml).

Example 104. No. [2- (5,7-Dichloro-3-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.011).

Using a procedure similar to that described in example 1, except for the use of 2amino-2-methyl-3- (5,7-dichloro-3-methyl-2H-indazol-2-yl) propionitrile (40 mg, described in example 103) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (64 mg, 92%). MS (ES): M / Ζ [M + H] = 487. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.83 (s, 3H), 2.73 (s, 3H), 5.00 (d, 1H), 5.06 (d, 1H), 7 45 (dd, 1 = 1.6 Hz, 1H), 7.87 (d, 1 = 8.2 Hz, 2H), 7.91 (dd, 1 = 1.6 Hz, 1H), 8.00 (d, 1 = 8.4 Hz, 2H) and 9.16 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.0 (s, 3P).

The compounds of examples 105-131 obtained according to the following General reaction scheme:

Final product:

US-K ₈ ; \\ 'S-N .; X = CB ₁₀ ; Y = CB ₁₁ ;

OS-K-; Ρ = Ν;

B ₂ = _O-C1-C4 alkyl, _{O-C1-C4 alkyl-O-C1-C4} alkyl, Ο-C1-C ₄ -NH-C 1-C ₄ alkyl, O-C1 C ₄ - (C 1 -C ₄ alkyl) 2;

B ₃ = B ₄ = H; a = 1; B ₅ = CH ₃ ; B ₆ = H;

Ζ = ί. ’(Ό); P- = p-phenyl-R.

Example 105. Ν- | 2- (6-Chloro-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.008).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (40 mg), the title compound was isolated as a white solid substances (60 mg, 88%). MS (ES): M / Ζ [M + H] = 453. ¹ H NMR: (400 MHz, DMSO-b6): 1.71 (s, 3H), 4.19 (s, 3H), 4.76 (d, 1H), 4.88 (d, 1H), 6 87 (dd, 1 = 9.0, 1.7 Hz, 1H), 7.50-7.55 (m, 3H), 7.89 (d, 1 = 9.1 Hz, 1H), 7, 97 (d, 1 = 8.8 Hz, 2H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

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2-amino-3- (6-chloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (475 mg, 93%) was obtained using a procedure similar to that described in example 1, part b, except use as starting material 1- (6-chloro-3-methoxy-2H-indazol-2-yl) propan-2-one (462 mg), which is prepared as follows.

a. To a solution of 4-chloro-2-nitrobenzaldehyde (4 g) in dioxane (35 ml), 2- (tert-butyldimethylsilanyloxy) propylamine (6.1 g, 1.5 eq.) In methanol (15 ml) was added followed by acetic acid (1 9 ml) in methanol (15 ml). After stirring at room temperature overnight, a molar solution of sodium cyanoborohydride in THF (22 ml) was added. After 30 minutes, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which is purified by chromatography (81O ₂ , heptane / EA) to obtain [2- (tert-butyldimethylsilanyloxy) propyl] (4-chloro-2-nitrobenzyl) amine (5.9 g, 77%). 2- (tert-Butyldimethylsilanyloxy) propylamine was obtained by reacting 1-aminopropan-2-ol with 2-tert-butyldimethylsilyl chloride and imidazole in DCM for 2 hours at room temperature, followed by treatment with water.

b. Potassium hydroxide (0.72 g) was added to a stirred solution of [2- (tert-butyldimethylsilanyloxy) propyl] - (4-chloro-2-nitrobenzyl) amine (3 g) in methanol (30 ml). After stirring at 60 ° C. overnight, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which is purified by chromatography (81O ₂ , heptane / EA) to obtain 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-3- methoxy-2H-indazole (2.2 g, 87%).

To a solution of 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-3-methoxy-2H-indazole (1 g) in THF (35 ml) was added a solution of tert-butylammonium fluoride (1 M in THF, 3 ml) . After stirring at room temperature for 1.5 hours, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to quantify 1- (6-chloro-3-methoxy-2H-indazol-2-yl) propan-2-ol as a solid (0.85 g )

b. A solution of dimethyl sulfoxide (1 ml) in DCM was added at -78 ° C to a solution of oxalyl chloride (0.6 ml) in DCM. After stirring for 30 minutes at −78 ° C., a solution of 1- (6-chloro-3-methoxy2H-indazol-2-yl) propan-2-ol (0.85 g) in DCM was added. After stirring for 30 minutes at -78 ° C, diisopropylethylamine (3.4 ml) was added and after another 30 minutes the reaction mixture was allowed to warm to room temperature for 1.5 hours before concentration under reduced pressure.

The remainder of the reaction mixture was transferred to a mixture of ethyl acetate and brine. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which is purified by chromatography (81O ₂ , heptane / EA) to obtain 1- (6-chloro-3-methoxy-2H-indazol-2-yl) propan-2-one as a solid (0.46 g, 55%).

Alternatively, the [2- (tert-butyldimethylsilanyloxy) propyl] - (4-chloro-2-nitrobenzyl) amine described in part a is prepared as follows.

c. To a suspension of 2- (tert-butyldimethylsilanyloxy) propylamine (9 eq.) In THF is slowly added

4-chloro-2-nitrobenzyl chloride in THF with vigorous stirring. After stirring at room temperature overnight, the mixture was concentrated under reduced pressure to give a residue, which was triturated with diethyl ether and filtered. The ether fraction was collected and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain [2- (tert-butyldimethylsilanyloxy) propyl] - (4-chloro-2 nitrobenzyl) amine.

Example 106. Ν- [2- (6-Chloro-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.009).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (40 mg, described in Example 105) and 4- trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (65 mg, 91%). MS (ES): M / Ζ [M + H] = 469. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.71 (s, 3H), 4.20 (s, 3H), 4.76 (d, 1H), 4.89 (d, 1H), 6 87 (dd, 1 = 9.0, 1.7 Hz, 1H), 7.51 (s, 1H), 7.86-7.91 (m, 3H), 7.97 (d, 2H) and 9.01 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -41.9 (s, 3P).

Example 107. No. [2- (5-Chloro-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.012).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (57 mg), the title compound was isolated as a white solid substances (84 mg, 86%). MS (ES): M / Ζ [M + H] = 453. ¹ H NMR: (400 MHz, DMSO-b6): 1.70 (s, 3H), 4.18 (s, 3H), 4.77 (d, 1H), 4.90 (d, 1H), 7 16 (dd, 1 = 9.3, 1.6 Hz, 1H), 7.46 (d, 1 = 9.2 Hz, 1H), 7.52 (d, 1 = 8.3 Hz, 2H) 7.94 (d, 1 = 0.9 Hz, 1H), 7.98 (d, 1 = 8.7 Hz, 2H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

2-amino-3- (6-chloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (114 mg, 73%) was obtained using a procedure similar to that described in example 1, part b, except use 1- (5

58 016912 chloro-3-methoxy-2H-indazol-2-yl) propan-2-one (140 mg). 1- (5-Chloro-3-methoxy-2H-indazol-2-yl) propan-2one is obtained using a procedure similar to that described in Example 105, part a-b, except for using 5-chloro-2-nitrobenzaldehyde (2 g) and sodium triacetoborohydride (3.4 g) in part a to obtain [2- (tert-butyldimethylsilanyloxy) propyl] - (5-chloro-2-nitrobenzyl) amine (2.2 g, 56%).

Example 108. N- [2- (5-Chloro-3-methoxy-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.013).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (5-chloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (57 mg described in example 107) and 4- trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (96 mg, 95%). MS (ES): M / Ζ [M + H] = 469. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.70 (s, 3H), 4.19 (s, 3H), 4.77 (d, 1H), 4.90 (d, 1H), 7 16 (d, 1 = 9.2 Hz, 1H), 7.46 (d, 1 = 9.4 Hz, 1H), 7.87 (d, 1 = 8.0 Hz, 2H), 7.92 -8.01 (m, 3H) and 9.00 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -41.9 (s, 3P).

Example 109. N- [2- (5-Chloro-3-ethoxy-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.014).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5-chloro-3-ethoxy-2H-indazol-2-yl) -2-methylpropionitrile (52 mg), the title compound was isolated as a white solid substances (85 mg, 97%). MS (ES): M / Ζ [M + H] = 467. ¹ H NMR: (400 MHz, DMSO-b6): 1.27 (t, 1 = 7.0 Hz, 3H), 1.71 (s, 3H), 4.52 (q, 1 = 6.9 Hz , 2H), 4.78 (d, 1H), 4.92 (d, 1H), 7.16 (dd, 1 = 9.3, 2.0 Hz, 1H), 7.47 (d, 1 = 9.3 Hz, 1H), 7.52 (d, 1 = 8.2 Hz, 2H), 7.87 (d, 1 = 1.5 Hz, 1H), 7.98 (d, 1 = 8, 8 Hz, 2H) and 8.91 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

2-amino-3- (5-chloro-3-ethoxy-2H-indazol-2-yl) -2-methylpropionitrile (104 mg, 72%) was obtained using a procedure similar to that described in example 1, part b, except using 1- (5-chloro-3-ethoxy-2H-indazol-2-yl) propan-2-one (131 mg) as the starting compound. 1- (5-Chloro-3-ethoxy-2H-indazol-2-yl) propan-2-one is obtained using a procedure similar to that described in Example 105, part a-b, except for using 5-chloro-2-nitrobenzaldehyde (2 g) and sodium triacetoxyborohydride (3.4 g) in part a and the use of ethanol instead of methanol in part b.

Example 110. N- [2- (5-Chloro-3-ethoxy-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.015).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (5-chloro-3-ethoxy-2H-indazol-2-yl) -2-methylpropionitrile (52 mg, described in Example 109) and 4- trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (83 mg, 93%). MS (ES): M / Ζ [M + H] = 483. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.26 (t, 1 = 7.0 Hz, 3H), 1.71 (s, 3H), 4.52 (q, 1 = 7.0 Hz , 2H), 4.78 (d, 1H), 4.93 (d, 1H), 7.16 (dd, 1 = 9.3, 1.9 Hz, 1H), 7.47 (d, 1 = 9.3 Hz, 1H), 7.85-7.89 (m, 3H), 7.96 (d, 1 = 8.8 Hz, 2H) and 8.99 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.0 (s, 3P).

Example 111. N- [1-Cyano-2- (3-methoxy-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.016).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (52 mg), the title compound was isolated as a white solid (140 mg , 77%). MS (ES): M / Ζ [M + H] = 419. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.72 (s, 3H), 4.19 (s, 3H), 4.77 (d, 1H), 4.90 (d, 1H), 6.88 (d, 1 = 1.2 Hz, 1H), 7.19 (d, 1 = 6.7 Hz, 1H), 7.41 (d, 1 = 8.9, Hz, 1H), 7 53 (d, 1 = 8.2 Hz, 2H), 7.82 (d, 1 = 8.6 Hz, 1H), 8.00 (d, 1 = 6.7 Hz, 2H) and 8.95 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

2-amino-3- (3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (130 mg, 83%) was obtained using the procedure similar to that described in example 1, part b, except for use as the starting material. 1- (3-methoxy-2H-indazol-2-yl) propan-2-one (138 mg). 1- (3-Methoxy-2Nindazol-2-yl) propan-2-one is obtained using a procedure similar to that described in Example 105, part a-b, except for using 2-nitrobenzaldehyde (2.5 g) as the starting material. in part a.

Example 112. Ν- {[2- (6-Chloro-3- (2-methoxyethoxy) -2H-indazol-2-yl) -1-cyano-1-methylethyl]} - 4-trifluoromethoxybenzamide (compound No. 2.017).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-3- (2-methoxyethoxy) -2H-indazol-2-yl) -2-methylpropionitrile (60 mg), the title compound was isolated. as a white solid (41 mg, 43%). MS (ES): M / Ζ [M + H] = 497. ¹ H NMR: (400 MHz, DMSO-b6): 1.70 (s, 3H), 3.27 (s, 3H), 3.61 (dd, 1 = 5.2, 3.7 Hz, 2H) 4.58 (dd, 1 = 4.9, 3.9 Hz, 2H), 4.79 (d, 1H), 4.92 (d, 1H), 6.90 (dd, 1 = 9.0 , 1.8 Hz, 1H), 7.53-7.55 (m, 3H), 7.82 (d, 1 = 9.1 Hz, 1H), 7.98 (d, 2H) and 8.93 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

2-amino-3- (6-chloro-3- (2-methoxyethoxy) -2H-indazol-2-yl) -2-methylpropionitrile (60 mg, 61%) was obtained using the procedure similar to that described in example 1, part B, with the exception of using 1- [6-chloro-3- (2-methoxyethoxy) -2H-indazol-2-yl] propan-2-one (90 mg) as the starting material. 1- [6-Chloro-3- (2-methoxyethoxy) -2H-indazol-2-yl] propan-2-one is obtained using a procedure similar to that described in Example 105, part a-b, except for using 2-methoxyethanol instead of methanol in part b.

- 59 016912

Example 113. Ν- {[2- (6-Chloro-3 - (2-dimethylaminoethoxy) -2H-indazol-2-yl) -1-cyano-1-methylethyl]} - 4 trifluoromethoxybenzamide (compound No. 2.018).

Using a procedure similar to that described in Example 1, except for using 2amino-3- (6-chloro-3- (2-dimethylaminoethoxy) -2H-indazol-2-yl) -2-methylpropionitrile (60 mg), the title compound was isolated as a white solid (44 mg, 46%). MS (ES): M / Ζ [M + H] = 510. ¹ H NMR: (400 MHz, chloroform-b): 1.90 (s, 3H), 2.43 (s, 6H), 2.85 (dd, 1 = 5.8, 4.8 Hz, 1H) 2.95 (dd, 1 = 6.9, 4.8 Hz, 1H), 4.52 (d, 1 = 14.2 Hz, 1H), 4.69 (ddd, 1 = 10.3, 5 7, 4.9 Hz, 1H), 4.80 (ddd, 1 = 10.2, 6.9, 4.7 Hz, 1H), 4.90 (d, 1 = 14.2 Hz, 1H) 6.92 (dd, 1 = 9.1, 1.7 Hz, 1H), 7.32 (d, 1 = 8.0 Hz, 2H), 7.47 (dd, 1 = 1.6, 0 6 Hz, 1H), 7.64 (dd, 1 = 9.0, 0.6 Hz, 1H) and 9.00 (s, 1H). ¹⁹ G NMR (376 MHz, chloroform-b): -58.1 (s, 3E).

2-amino-3 - (6-chloro-3- (2-dimethylaminoethoxy) -2H-indazol-2-yl) -2-methylpropionitrile (127 mg, 78%) was obtained using a procedure similar to that described in example 1, part B, with the exception of using 1- [6-chloro-3- (2-dimethylaminoethoxy) -2H-indazol-2yl)] propan-2-one (150 mg) as the starting material. 1- [6-Chloro-3- (2-dimethylaminoethoxy) -2H-indazol-2-yl] propan-2-one is obtained using a procedure similar to that described in example 105, part a-b, except for the use of 2-dimethylaminoethanol instead of methanol in part b.

Example 114. No. [1-Cyano-2- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.020).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (196 mg), the title compound was isolated as white solid (147 mg, 46%). MS (ES): M / Ζ [M + H] = 487. ¹ H NMR: (400 MHz, chloroform-b): 1.96 (s, 3H), 4.42 (s, 3H), 4.53 (d, 1 = 14.2 Hz, 1H), 4.88 (d, 1 = 14.2 Hz, 1H), 7.31 (d, 2H), 7.35 (d, 1 = 1.7 Hz, 1H), 7.68 (d, 1 = 1.7 Hz , 1H), 8.01-8.10 (m, 2H) and 9.13 (s, 1H). Я NMR (376 MHz, chloroform-b): -58.1 (s, 3E).

2-amino-3- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile was obtained using the procedure similar to that described in example 1, part b, except for using as starting material 1- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) propan-2-one. 1- (4,6-Dichloro-3-methoxy2H-indazol-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, part a-b, except for the use of 3,5-dichloro-2 -nitrobenzaldehyde (2.1 g) and decaborane (0.41 g) in part a to obtain [2- (tert-butyldimethylsilanyloxy) propyl] - (3,5-dichloro-2-nitrobenzyl) amine (1.2 g, 32%). 3,5-Dichloro-2-nitrobenzaldehyde (2.2 g, 79%) is obtained by nitration of 3,5-dichlorobenzaldehyde (2.2 g) in a mixture of nitric acid (1.5 ml) and sulfuric acid (8 ml) at 0 ° C within 30 minutes

Example 115. No. [1-Cyano-2- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.019).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (181 mg, described in example 114) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (161 mg, 51%). MS (ES): M / Ζ [M + H] = 503. ^! H NMR: (400 MHz, chloroform-b): 1.96 (s, 3H), 4.42 (s, 3H), 4.53 (d, 1 = 14.2 Hz, 1H), 4.88 ( d, 1 = 14.2 Hz, 1H), 7.35 (d, 1 = 1.7 Hz, 1H), 7.68 (d, 1 = 1.7 Hz, 1H), 7.75 (d, 1 = 8.2 Hz, 2H), 8.02-8.09 (m, 2H) and 9.21 (s, 1H). Я NMR (376 MHz, chloroform-b): -42.4 (s, 3E).

Example 116. No. [1-Cyano-2- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.021).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (4,6-dichloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (30 mg), the title compound was isolated as white solid (45 mg, 92%). MS (ES): M / Ζ [M + H] = 487. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.75 (s, 3H), 4.12 (s, 3H), 4.94 (s, 2H), 7.17 (d, 1 = 1 , 3 Hz, 1H), 7.53 (d, 1 = 8.2 Hz, 2H), 7.63 (d, 1 = 1.2 Hz, 1H), 7.98 (d, 1 = 8.7 Hz, 2H) and 8.95 (s, 1H). Я NMR (376 MHz, DMSO-b ₆ ): -57.1 (s, 3E).

2-amino-3- (4,6-dichloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (60 mg, 32%) was obtained using the procedure similar to that described in example 1, part b, with the exception of using 1- (4,6-dichloro-3-methoxy-2H-indazol-2-yl) propan-2-one (170 mg) as the starting material. 1- (4,6-Dichloro-3-methoxy-2H-indazol-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, part a-b, except for the use of 2,4-dichloro-6 -nitrobenzaldehyde (1 g) in part a to obtain [2- (tert-butyldimethylsilanyloxy) propyl] - (2,4-dichloro-6-nitrobenzyl) amine (0.6 g, 37%). 2,4-Dichloro-6-nitrobenzaldehyde is prepared as follows.

To a solution of 1,3-dichloro-5-nitrobenzene (7.7 g) and chloroform (4 ml) in a mixture of THF and DMX (1: 1.5, 100 ml), a unimolar solution of sodium hexamethyldisilazane (No. 1 NME8) was slowly added at -78 ° C. ) in THF (7.7 ml). After stirring for 30 minutes, the reaction was quenched at -78 ° C with a methanolic solution of hydrochloric acid and allowed to warm to room temperature. The reaction mixture was extracted with ethyl acetate. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue that contains 70% 1,5-dichloro-2-dichloromethyl-3-nitrobenzene.

A mixture of 1,5-dichloro-2-dichloromethyl-3-nitrobenzene (5.8 g, 70% purity) and zinc dichloride in ant

- 60 016912 other acid (85%) is heated at the boil under reflux for 14 hours. The reaction mixture is extracted with ethyl acetate. The organic phase was concentrated under reduced pressure to obtain a residue, which was poured into water and extracted with ethyl acetate. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which is purified by chromatography (81O ₂ , heptane / EA) to obtain 2,4-dichloro-6 nitrobenzaldehyde as a solid (2.9 g, 87% purity). ¹ H NMR: (400 MHz, chloroform-4): 7.76 (d, 1 = 1.9 Hz, 1H), 7.93 (d, 1 = 1.9 Hz, 1H) and 10.32 (s , 1H).

Example 117. No. [1-Cyano-2- (4,6-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.022).

When using a procedure similar to that described in example 1, except for the use of 2 amino-3- (4,6-dichloro-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (30 mg, described in example 116) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (42 mg, 83%). MS (ES): M / Ζ [M + H] = 503. ^! H NMR: (400 MHz, DMSO-46): 1.75 (s, 3H), 4.12 (s, 3H), 4.94 (d, 1 = 6.5 Hz, 2H), 7.17 ( d, 1 = 1.2 Hz, 1H), 7.62 (d, 1 = 1.1 Hz, 1H), 7.86-7.91 (m, 2H), 7.93-7.99 (m , 2H) and 9.03 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-46): -41.9 (s, 3P).

Example 118. No. [2- (6-Bromo-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.023).

Using a procedure similar to that described in Example 1, with the exception of using 2amino-3- (6-bromo-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (50 mg), the title compound was isolated as a white solid substances (73 mg, 90%). MS (ES): M / Ζ [M + H] = 497. ¹ H NMR: (400 MHz, DMSO-4 ₆ ): 1.71 (s, 3H), 4.19 (s, 3H), 4.76 (d, 1H), 4.88 (d, 1H), 6.97 (dd, 1 = 9.0, 1.4 Hz, 1H), 7.53 (d, 1 = 8.3 Hz, 2H), 7.68 (d, 1 = 0.8 Hz, 1H ), 7.83 (d, 1 = 9.1 Hz, 1H), 7.98 (d, 1 = 8.7 Hz, 2H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-46): -57.1 (s, 3P).

2-amino-3- (6-bromo-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile was prepared using the procedure similar to that described in example 1, part b, except for using 1- as the starting material. (6-bromo-3-methoxy-2H-indazol-2-yl) propan-2-one. 1- (6-Bromo-3-methoxy-2H-indazol2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, part a-4, except for using 4-bromo-2-nitrobenzaldehyde (5 , 1 g) and decaborane (0.81 g) in part a to obtain [2- (tert-butyldimethylsilanyloxy) propyl] - (4-bromo-2-nitrobenzyl) amine (3.4 g).

Example 119. No. [2- (6-Bromo-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.024).

When using a procedure similar to that described in example 1, except for the use of 2amino-3- (6-bromo-3-methoxy-2H-indazol-2-yl) -2-methylpropionitrile (50 mg described in example 118), and 4 trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (80 mg, 96%). MS (ES): M / Ζ [M + H] = 513. Ή NMR: (400 MHz, DMSO-4 ₆ ): 1.71 (s, 3H), 4.19 (s, 3H), 4.77 (d, 1H), 4.89 (d, 1H), 6 97 (dd, 1 = 9.1, 1.5 Hz, 1H), 7.68 (d, 1 = 0.9 Hz, 1H), 7.83 (d, 1 = 9.1 Hz, 1H) 7.86-7.91 (m, 2H), 7.94-7.99 (m, 2H) and 9.00 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-4 ₆ ): -41.9 (s, 3P).

Example 120. No. [1-Cyano-2- (3-methoxy-6-trifluoromethyl-2H-indazol-2-yl) -1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 2.025)

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (3-methoxy-6-trifluoromethyl-2H-indazol-2-yl) -2-methylpropionitrile (50 mg), the title compound was isolated as a white solid substances (62 mg, 77%). MS (ES): M / Ζ [M + H] = 487. ¹ H NMR: (400 MHz, DMSO-4 ₆ ), 1.72 (s, 3H), 4.23 (s, 3H), 4.85 (d, 1H), 4.97 (d, 1H), 7.08 (dd, 1 = 9.0, 1.1 Hz, 1H), 7.53 (d, 1 = 8.2 Hz, 2H), 7.86 (s, 1H), 7.99 (d , 1 = 8.8 Hz, 2H), 8.09 (d, 1 = 9.0 Hz, 1H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-46): -61.8 (s, 3P) and -57.1 (s, 3P).

2-amino-3- (3-methoxy-6-trifluoromethyl-2H-indazol-2-yl) -2-methylpropionitrile was prepared using the procedure similar to that described in example 1, part b, as starting material 1- (3methoxy) -6-trifluoromethyl-2H-indazol-2-yl) propan-2-one. 1- (3-Methoxy-6-trifluoromethyl-2H-indazol-2yl) propan-2-one is obtained using a procedure similar to that described in Example 105, part a-4, except for using 2-nitro-4- (trifluoromethyl) benzaldehyde (1 d) in part a to obtain [2 (tert-butyldimethylsilanyloxy) propyl] - (2-nitro-4- (trifluoromethyl) benzyl) amine (0.6 g, 33%).

Example 121. No. [1-Cyano-2- (3-methoxy-6-trifluoromethyl-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.026).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (3-methoxy-6-trifluoromethyl-2H-indazol-2-yl) -2-methylpropionitrile (50 mg, described in example 120) and 4- trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (66 mg, 78%). MS (ES): M / Ζ [M + H] = 503. ^! H NMR: (400 MHz, DMSO-46): 1.72 (s, 3H), 4.24 (s, 3H), 4.84 (d, 1 = 13.8 Hz, 1H), 4.96 ( d, 1 = 13.9 Hz, 1H), 7.08 (dd, 1 = 9.0, 1.4 Hz, 1H), 7.85 (s, 1H), 7.88 (d, 1 = 8 , 2 Hz, 2H), 7.94-7.99 (m, 2H), 8.09 (d, 1 = 9.0 Hz, 1H) and 8.99 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-46): -42.0 (s, 3P) and -61.8 (s, 3P).

Example 122. No. [2- (6-Chloro-3-ethoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.027).

- 61 016912

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-3-ethoxy-2H-indazol-2-yl) -2-methylpropionitrile (113 mg), the title compound was isolated as a white solid substances (95 mg, 50%). MS (ES): M / Ζ [M + H] = 467. ¹ H NMR: (400 MHz, chloroform-ά): 1.58 (t, 1 = 7.1 Hz, 3H), 1.91 (s, 3H), 4.50 (d, 1 = 14.2 Hz , 1H), 4.63-4.81 (m, 2H), 4.83 (d, 1 = 14.1 Hz, 1H), 6.92 (dd, 1 = 9.1, 1.7 Hz, 1H), 7.34 (d, 1 = 8.1 Hz, 2H), 7.46 (d, 1 = 1.1 Hz, 1H), 7.62 (d, 1 = 9.1 Hz, 1H) 7.89-8.02 (m, 2H); and 9.07 (s, 1H). ¹⁹ E NMR (376 MHz, chloroform-ά): -58.1 (s, 3E).

2-amino-3- (6-chloro-3-ethoxy-2H-indazol-2-yl) -2-methylpropionitrile (221 mg, 95%) was obtained using a procedure similar to that described in example 1, part b, except use of 1- (6chlor-3-ethoxy-2H-indazol-2-yl) propan-2-one (210 mg). 1- (6-Chloro-3-ethoxy-2H-indazol-2-yl) propan-2-one is obtained using a procedure similar to that described in Example 105, part a-ά, except for using 4-chloro-2-nitrobenzaldehyde (21.7 g) and decaborane (4.2 g) in part a and the use of ethanol instead of methanol in part b.

Example 123. Ν- | 2- (6-Chloro-3-ethoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.028).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (6-chloro-3-ethoxy-2H-indazol-2-yl) -2-methylpropionitrile (108 mg described in example 122) and 4- trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (96 mg, 51%). MS (ES): M / Ζ [M + H] = 483. Ή NMR: (400 MHz, chloroform-ά): 1.59 (t, 1 = 7.0 Hz, 3H), 1.91 (s, 3H), 4.50 (d, 1 = 14.2 Hz, 1H), 4.63-4.81 (m, 2H), 4.83 (d, 1 = 14.2 Hz, 1H), 6.92 (dd, 1 = 9.1, 1.7 Hz, 1H ), 7.47 (d, 1 = 1.2 Hz, 1H), 7.62 (d, 1 = 9.0 Hz, 1H), 7.79 (d, 1 = 8.3 Hz, 2H), 7.90-7.99 (m, 2H) and 9.15 (s, 1H). ¹⁹ E NMR (376 MHz, chloroform-ά): -42.3 (s, 3E).

Example 124. No. [2- (6-Chloro-3-propoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.029).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-3-propoxy-2H-indazol-2-yl) -2-methylpropionitrile (103 mg), the title compound was isolated as a white solid substances (104 mg, 54%). MS (ES): M / Ζ [M + H] = 481. ¹ H NMR: (400 MHz, chloroform-ά): 1.14 (t, 1 = 7.4 Hz, 3H), 1.90 (s, 3H), 1.92-2.03 (m, 2H) 4.51 (d, 1 = 14.1 Hz, 1H); 4.55-4.69 (m, 2H); 4.81 (d, 1 = 14.1 Hz; 1H); 6.91 ( dd, 1 = 9.1, 1.7 Hz, 1H), 7.34 (dd, 1 = 8.8, 0.8 Hz, 2H), 7.46 (dd, 1 = 1.7, 0, 6 Hz, 1H), 7.62 (dd, 1 = 9.1, 0.6 Hz, 1H), 7.90-8.01 (m, 2H) and 9.10 (s, 1H). ¹⁹ E NMR (376 MHz, chloroform-ά): -58.1 (s, 3E).

2-amino-3- (6-chloro-3-propoxy-2H-indazol-2-yl) -2-methylpropionitrile (207 mg, 92%) was obtained using a procedure similar to that described in example 1, part b, except use as starting material 1- (6-chloro-3-propoxy-2H-indazol-2-yl) propan-2-one (205 mg). 1- (6-Chloro-3-propoxy-2H-indazol-2-yl) -propan-2-one is obtained using a procedure similar to that described in Example 105, part a-ά, except for using 4-chloro-2-nitrobenzaldehyde (21 , 7 g) and decaborane (4.2 g) in part a and the use of n-propanol instead of methanol in part b.

Example 125. No. [2- (6-Chloro-3-propoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.030).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-3-propoxy-2H-indazol-2-yl) -2-methylpropionitrile (104 mg described in Example 124) and 4- trifluoromethylthiobenzoyl chloride), the title compound is isolated as a white solid (104 mg, 54%). MS (ES): M / Ζ [M + H] = 497. Ί1 NMR: (400 MHz, chloroform-ά): 1.14 (t, 1 = 7.4 Hz, 3H), 1.90 (s, 3H), 1.92-2.04 (m, 2H), 4.51 (d, 1 = 14.2 Hz, 1H), 4.56-4.70 (m, 2H), 4.82 (d, 1 = 14.2 Hz, 1H), 6.92 (dd , 1 = 9.1, 1.7 Hz, 1H), 7.47 (d, 1 = 1.7 Hz, 1H), 7.62 (dd, 1 = 9.1, 0.5 Hz, 1H) 7.79 (dd, 1 = 8.3 Hz, 2H), 7.91-7.99 (m, 2H) and 9.17 (s, 1H). ¹⁹ E NMR (376 MHz, chloroform-ά): -42.3 (s, 3E).

Example 126. No. [2- (6-Chloro-3-butoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.031).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-3-butoxy-2H-indazol-2-yl) -2-methylpropionitrile (88 mg), the title compound was isolated as a white solid substances (60 mg, 43%). MS (ES): M / Ζ [M + H] = 495. ¹ H NMR: (400 MHz, chloroform-ά): 1.04 (t, 1 = 7.4 Hz, 3H), 1.51-1.65 (m, 2H), 1.89 (s, 3H) 1.89-1.98 (m, 2H), 4.51 (d, 1 = 14.2 Hz, 1H), 4.57-4.73 (m, 2H), 4.81 (d, 1 = 14.2 Hz, 1H), 6.91 (dd, 1 = 9.1, 1.7 Hz, 1H), 7.34 (d, 1 = 8.0 Hz, 2H), 7.46 (d , 1 = 1.1 Hz, 1H), 7.62 (dd, 1 = 9.1, 0.5 Hz, 1H), 7.91-8.00 (m, 2H) and 9.09 (s, 1H). ¹⁹ E NMR (376 MHz, chloroformά): -58.1 (s, 3E).

2-amino-3- (6-chloro-3-butoxy-2H-indazol-2-yl) -2-methylpropionitrile (88 mg) was obtained using the procedure similar to that described in example 1, part b, except for use as starting material 1- (6-chloro-3-butoxy-2H-indazol-2-yl) propan-2-one (79 mg). 1- (6-Chloro-3butoxy-2H-indazol-2-yl) propan-2-one is obtained using a procedure similar to that described in Example 105, part a-за, except for using 4-chloro-2-nitrobenzaldehyde (21 , 7 g) and decaborane (4.2 g) in part a and the use of butanol instead of methanol in part b.

- 62 016912

Example 127. 2- [2-Cyano-2-methyl-2- (4-trifluoromethoxybenzoylamino) ethyl] -3methoxy-2H-indazole-6-carboxylic acid methyl ester (compound No. 2.032).

Using a procedure similar to that described in Example 1, except for the use of 2- (2-amino-2-cyano-2-methylethyl) -3-methoxy-2H-indazole-6-carboxylic acid methyl ester (88 mg), title compound isolated as a white solid (126 mg, 86%). MS (ES): M / Ζ [M + H] = 477. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.72 (s, 3H), 3.87 (s, 3H), 4.21 (s, 3H), 4.83 (d, 1H), 4 97 (d, 1H), 7.37 (d, 1 = 8.9 Hz, 1H), 7.53 (d, 1 = 8.3 Hz, 2H), 7.93-8.03 (m, 3H), 8.07 (s, 1H) and 8.92 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b6): -57.1 (s, 3E).

2- (2-amino-2-cyano-2-methylethyl) -3-methoxy-2H-indazole-6-carboxylic acid methyl ester was obtained using the procedure similar to that described in example 1, part b, except for use as the starting material. 3-methoxy-2- (2-oxopropyl) -2H-indazole-6-carboxylic acid methyl ester. 3-Methoxy-2- (2-oxopropyl) -2H-indazole-6-carboxylic acid methyl ester was obtained using the procedure similar to that described in Example 105, part a-b, except for the use of 4-formyl-3-nitrobenzoic methyl ester acid (2 g) in part a to obtain 4 - {[2- (tert-butyldimethylsilanyloxy) propylamino] methyl} -3-nitrobenzoic acid methyl ester (2.83 g, 77%). In the main cyclization step in part b, the desired 2- [2- (tert-butyldimethylsilanyloxy) propyl] -3-methoxy-2H-indazole-6-carboxylic acid methyl ester (230 mg) is isolated together with 2- [2- (tert-butyldimethylsilanyloxy) propyl] -3-hydroxy-2H-indazole-6-carboxylic acid (781 mg).

Example 128. No. [1-Cyano-2- (3-methoxy-6-nitro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.033).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (3-methoxy-6-nitro-2H-indazol-2-yl) -2-methylpropionitrile (63 mg), the title compound was isolated as a white solid substances (84 mg, 79%). MS (ES): M / Ζ [M + H] = 464. ¹ H NMR: (400 MHz, DMSO-b ₆ ): 1.73 (s, 3H), 4.25 (s, 3H), 4.88 (d, 1H), 5.00 (d, 1H), 7.53 (d, 1 = 8.3 Hz, 2H), 7.61 (dd, 1 = 9.3, 1.9 Hz, 1H), 7.99 (d, 1 = 8.7 Hz, 2H ), 8.12 (d, 1 = 9.3 Hz, 1H), 8.42 (d, 1 = 1.6 Hz, 1H) and 8.93 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b6): -57.1 (s, 3E).

2-amino-3- (3-methoxy-6-nitro-2H-indazol-2-yl) -2-methylpropionitrile was prepared using the procedure similar to that described in example 1, part b, except for using 1- as the starting material. (3-methoxy-6-nitro-2H-indazol-2-yl) propan-2-one. 1- (3-Methoxy-6-nitro-2Nindazol-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, part a-b, except for the use of 2,4-dinitrobenzaldehyde (2 g) in part a to obtain [2 (tert-butyldimethylsilanyloxy) propyl] - (2,4-dinitrobenzyl) amine (2.6 g, 64%).

Example 129. No. [2- (6-amino-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.034).

A mixture of No. [2-cyano-2- (3-methoxy-6-nitro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (30 mg) described in example 128, and palladium on charcoal in methanol (2 ml) was stirred at room temperature in a hydrogen atmosphere for 2.5 hours. The reaction mixture was filtered through a layer of CeChe® and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain the title compounds in the form of a white solid (18 mg, 64%). MS (ES): M / Ζ [M + H] = 434. Ή NMR: (400 MHz, chloroform-b): 1.88 (s, 3H), 4.38 (s, 3H), 4.41 (d, 1H), 4.72 (d, 1 = 14.2 Hz, 1H), 6.48 (dd, 1 = 9.0, 1.8 Hz, 1H), 6.53 (d, 1 = 1.2 Hz, 1H), 7.31 (d, 1 = 8 , 3 Hz, 2H), 7.55 (d, 1 = 9.0 Hz, 1H), 7.98 (d, 1 = 8.8 Hz, 2H) and 9.43 (s, 1H). ¹⁹ E NMR (376 MHz, chloroform-b): -58.0 (s, 3E).

Example 130. No. [2- (6-Acetylamino-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.035).

Using a procedure similar to that described in Example 1, except for the use of Ν [2- (6-amino-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (23 mg described in Example 129) and acetyl chloride, the title compound was isolated as a white solid (8 mg, 32%). MS (ES): M / Ζ [M + H] = 476. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.71 (s, 3H), 2.05 (s, 3H), 4.16 (s, 3H), 4.71 (d, 1H), 4 82 (d, 1H), 6.88 (dd, 1 = 9.2, 1.6 Hz, 1H), 7.52 (d, 1 = 8.0 Hz, 2H), 7.74 (d, 1 = 9.1 Hz, 1H),

7.86 (s, 1H), 7.99 (d, 1 = 8.8 Hz, 2H), 8.95 (s, 1H) and 9.89 (s, 1H). ¹⁹ E NMR (376 MHz, DMSO-b ₆ ): -57.1 (s, 3E).

Example 131. Methyl 2- [2-cyano-2-methyl-2- (4-trifluoromethoxybenzoylamino) ethyl] -3-methoxy-2-indazole-6-carboxamide (compound No. 2.036).

A solution of 2- [2-cyano-2-methyl-2- (4-trifluoromethoxybenzoylamino) ethyl] -3-methoxy2H-indazole-6-carboxylic acid methyl ester (50 mg, described in Example 127) in methanol (3 ml) was stirred with ammonium hydroxide (1.5 ml) at room temperature for 8 days. The reaction mixture was concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound as a white solid (3 mg). MS (ES): M / Ζ [M + H] = 462. Ή NMR: (400 MHz, methanol-b ₄ ): 1.81 (s, 3H), 4.32 (s, 3H), 4.82 (d, 1H), 5.08 (d, 1 = 14, 0 Hz, 1H),

7.38 (dd, 1 = 9.0, 1.4 Hz, 1H), 7.42 (d, 1 = 8.6 Hz, 2H), 7.90 (d, 1 = 9.0 Hz, 1H ), 7.97 (d, 1 = 8.9 Hz, 2H) and 7.99 (s, 1H). ¹⁹ E NMR (376 MHz, methanol-b ₄ ): -59.8 (s, 3E).

- 63 016912

The compounds of examples 132-137 obtained according to the following General reaction scheme:

Final product:

ν ^ -B ^ No. CH; X = CB ₁₀ ; Υ ^^;

SI-11; P = K;

B ₃ = Vd = H; a = 1; B ₅ = CH ₃ ; 17.11;

7 = C (O); B ₇ = p-phenyl-B.

Example 132. No. [2- (6-Chloro-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.037).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-2H-indazol-2-yl) -2-methylpropionitrile (20 mg), the title compound was isolated as a white solid (34 mg , 93%). MS (ES): M / Ζ [M + H] = 423. ¹ H NMR: (400 MHz, chloroform): 1.95 (s, 3H), 4.81 (d, 1H), 4.89 (d, 1H), 7.11 (dd, 1 = 8.9, 1.7 Hz, 1H), 7.33 (d, 1 = 8.4 Hz, 2H), 7.65 (d, 1 = 8.9 Hz, 1H), 7.69 (s, 1H), 7 90 (d, 1 = 8.7 Hz, 2H), 8.17 (s, 1H) and 8.49 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-3- (6-chloro-2H-indazol-2-yl) -2-methylpropionitrile (54 mg, 79%) was obtained using a procedure similar to that described in example 1, part b, except for using 1- ( 6-chloro-2Nindazol-2-yl) propan-2-one (68 mg). 1- (6-Chloro-2H-indazol-2-yl) propan-2-one is obtained using a procedure similar to that described in Example 105, parts c and b, except for the use of [2- (tert-butyldimethylsilanyloxy) as the starting material ) propyl] -6-chloro-2H-indazole obtained as follows.

A mixture of [2- (tert-butyldimethylsilanyloxy) propyl] - (4-chloro-2-nitrobenzyl) amine (4.6 g described in Example 105, part a) and zinc (2 g) in ethanol (95%, 20 ml ) and one drop of acetic acid is heated at 60 ° C for 24 hours. The reaction mixture is filtered through a layer of CeChe® and concentrated under reduced pressure to obtain a residue, which is purified by chromatography (81O ₂ , heptane / EA) to obtain 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-2H-indazole as a white solid (0.9 g, 22%) along with the regenerated starting material (2.2 g, 48%).

Example 133. No. [2- (6-Chloro-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.038).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-2H-indazol-2-yl) -2-methylpropionitrile (20 mg described in Example 132) and 4 trifluoromethylthiobenzoyl chloride, the title compound was isolated in as a white solid (37 mg, 98%). MS (ES): M / Ζ [M + H] = 439. ^! H NMR: (400 MHz, chloroform-b): 1.95 (s, 3H), 4.81 (d, 1H), 4.89 (d, 1H), 7.12 (dd, 1 = 9.0 1.6 Hz, 1H), 7.65 (d, 1 = 9.0, 1H), 7.69 (s, 1H), 7.78 (d, 1 = 8.3 Hz, 2H), 7 89 (d, 1 = 8.3 Hz, 2H), 8.18 (s, 1H) and 8.58 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -42.2 (s, 3P).

Example 134. No. [1-Cyano-2- (4,6-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.040).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (4,6-dichloro-2H-indazol-2-yl) -2-methylpropionitrile (20 mg), the title compound was isolated as a white solid ( 31 mg, 91%). MS (ES): M / Ζ [M + H] = 457. ¹ H NMR: (400 MHz, chloroform-b): 1.96 (s, 3H), 4.82 (d, 1H), 4.92 (d, 1H), 7.15 (d, 1 = 1, 3 Hz, 1H), 7.34 (d, 1 = 8.2 Hz, 2H), 7.60 (s, 1H), 7.89 (d, 1 = 8.8 Hz, 2H) and 8.22 (s, 2H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-3- (4,6-dichloro-2H-indazol-2-yl) -2-methylpropionitrile (88 mg, 54%) was obtained using the procedure similar to that described in example 1, part b, except for use in as the starting material, 1- (4,6-dichloro-2H-indazol-2-yl) propan-2-one (146 mg). 1- (4,6-Dichloro-2H-indazol-2yl) propan-2-one is obtained using a procedure similar to that described in Example 105, parts c and b, except for using 2- [2- (tert-butyldimethylsilanyloxy) as the starting material ) propyl] -4,6-dichloro-2H-indazole, which is obtained using a procedure similar to that described in example 132, part a, and with the exception of using as an outcome

- 64 016912 of the substance [2- (tert-butyldimethylsilanyloxy) propyl] - (2,4-dichloro-6-nitrobenzyl) amine described in Example 116.

Example 135. N- [1-Cyano-2- (4,6-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.041).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (4,6-dichloro-2H-indazol-2-yl) -2-methylpropionitrile (20 mg, described in example 134) and 4 trifluoromethylthiobenzoyl chloride, title compound isolated as a white solid (34 mg, 97%). MS (ES): M / Ζ [M + H] = 473. Ή NMR: (400 MHz, chloroform-b): 1.96 (s, 3H), 4.82 (d, 1H), 4.93 (d, 1H), 7.15 (d, 1 = 0.9 Hz, 1H), 7.60 (s, 1H), 7.79 (d, 2H), 7.88 (d, 2H), 8.22 (s, 1H) and 8.32 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -42.2 (s, 3P).

Example 136. No. [1-Cyano-1-methyl-2- (4,6,7-trichloro-2H-indazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 2.048).

Using a procedure similar to that described in Example 1, except for the use of 2amino-2-methyl-2- (4,6,7-trichloro-2H-indazol-2-yl) propionitrile (60 mg), the title compound was isolated as white solid (34 mg, 35%), IG = 0.65 (1: 1 EA / heptane). ¹ H NMR: (400 MHz, DMSObe): 1.70 (s, 3H), 5.12 (d, 1H), 5.24 (d, 1H), 7.47 (s, 1H), 7.52 (d, 1 = 8.1 Hz, 2H), 7.97 (d, 1 = 8.8 Hz, 2H), 8.72 (s, 1H) and 8.92 (s, 1H). ¹⁹ B NMR (376 MHz, DMSO-b ₆ ): -57.1 (s, 3P).

2-amino-2-methyl-2- (4,6,7-trichloro-2H-indazol-2-yl) propionitrile (0.16 g, 60%) was obtained using a procedure similar to that described in example 1, part b , with the exception of using 1- (4,6,7-trichloro-2H-indazol-2-yl) propan-2-one (0.25 g) as the starting material. 1- (4,6,7-Trichloro-2-Indindazol-2-yl) propan-2-one is obtained using a procedure similar to that described in Example 105, parts c and b, except for using 2- [2- as the starting material (tert-butyldimethylsilanyloxy) propyl] -4,6,7-trichloro-2H-indazole (1.4 g, 69%), which was obtained using a procedure similar to that described in example 132, part a, except for using as starting material [ 2- (tert-butyldimethylsilanyloxy) propyl] - (2-nitro-3,4,6trichlorobenzyl) amine (2.2 g). [2- (tert-Butyldimethylsilanyloxy) propyl] - (2-nitro-3,4,6trichlorobenzyl) amine (2.2 g, 44%) was obtained using a procedure similar to that described in example 105, part a, except for use in as the starting material, 2-nitro-3,4,6 trichlorobenzaldehyde (3 g), which is obtained as follows.

a. To a mixture of 2-nitro-3,4,6-trichloroaniline (57 g) described in Example 39, part ac, and copper bromide (P) (105 g) in acetonitrile (1 L), tert-butyl nitrite (90 %, 37 ml) and the mixture is heated to 60 ° C. overnight. The reaction mixture was filtered through a Ce1e® layer, washed with ethyl acetate, and the filtrates were concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 2-bromo-3-nitro-1,4,5-trichlorobenzene (53 g, 74%). IG = 0.8 (1: 4 EA / heptane).

b. 2-Bromo-3-nitro-1,4,5-trichlorobenzene (53 g), tributyl vinyltin (58 ml, 62 g) and [1,1'-bis (diphenylphosphine) ferrocene] dichloropalladium (P), complex with DCM ( 1: 1) (14 g) was heated in toluene (400 ml) at 100 ° C for 24 hours. The mixture was concentrated under reduced pressure, transferred to ethyl acetate (1 L) and treated with saturated potassium fluoride solution (300 ml) overnight . The mixture was filtered through a Ce1e® layer, the organic layer was separated and dried over sodium sulfate, washed with ethyl acetate and the filtrates were concentrated under reduced pressure, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 3- nitro-1,2,5-trichloro-4-vinylbenzene as a white solid (34 g, 78%). IG = 0.75 (1: 4 EA / heptane).

c. A solution of 3-nitro-1,2,5-trichloro-4-vinylbenzene (27 g) in a mixture of DCM and methanol (3: 1, 300 ml) was treated with gaseous ozone for 2 hours at -78 ° C. The mixture was purged with oxygen for 10 minutes, then quenched with dimethyl sulfide (2 ml) at -78 ° C. The mixture was allowed to warm to 0 ° C, treated with 10% sodium thiosulfate solution (200 ml), then diluted with additional DCM. The organic layer was collected, dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 2-nitro3,4,6-trichlorobenzaldehyde as a white solid (20 g, 74%). IG = 0.5 (3: 8 EA / heptane). ¹ H NMR: (400 MHz, DMSO-b ₆ ): 8.44 (s, 1H) and 10.17 (s, 1H).

Example 137. N- [1-Cyano-1-methyl-2- (4,6,7-trichloro-2H-indazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 2.049).

Using a procedure similar to that described in Example 1, except for the use of 2amino-2-methyl-3- (4,6,7-trichloro-2H-indazol-2-yl) propionitrile (60 mg described in Example 136) and 4 trifluoromethylthiobenzoyl chloride , the title compound is isolated as a white solid (40 mg, 40%). IG = 0.65 (1: 1 EA / heptane). Ή NMR: (400 MHz, DMSO-b ₆ ): 1.70 (s, 3H), 5.11 (d, 1H), 5.25 (d, 1H), 7.47 (s, 1H), 7 79-7.80 (m, 4H), 8.73 (s, 1H) and 9.00 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -42.0 (s, 3P).

- 65 016912

The compounds of examples 138-144 were prepared according to the following general reaction scheme:

Final product:

ν = ^; W = CH; X = C-B ^; Υ = € -Κ _η ;

SI-1V-; P = I;

B ₃ = B ₄ = H; a = 1; B ₅ = CH ₃ ; B ₆ = H;

Ζ = Ο (Ό); B ₇ = p-phenyl-B.

Example 138. Ν- [1-Cyano-1-methyl-2- (3,6,7-trichloro-2H-indazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 2.039).

A mixture of No. [2- (6-chloro-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (25 mg described in Example 132) and Ν-chlorosuccinimide (50 mg) in acetonitrile (2 ml) was heated to 60 ° C. overnight. The mixture was concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound (22 mg, 75%) with 70% purity together with 30% of another isomer. MS (ES): M / Ζ [M + H] = 491. ¹ H NMR: (400 MHz, chloroform-6): 1.96 (s, 3H), 4.81 (d, 1 = 14.3 Hz, 1H), 5.06 (d, 1 = 14.3 Hz , 1H), 7.25 (d, 1 = 8.9 Hz, 1H), 7.32 (dd, 1 = 8.1, 0.9 Hz, 2H), 7.51 (d, 1 = 8, 9 Hz, 1H), 8.05 (d, 1 = 8.9 Hz, 2H) and 8.92 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-6): -58.1 (s, 3P).

Example 139. Ν- [2- (3-Bromo-6-chloro-2H-indazol-2-yl)] -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.042).

Mixture of No. [2- (6-chloro-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (25 mg described in Example 132) and Ν-bromosuccinimide (10 mg) in acetonitrile (1 ml) was heated to 60 ° C for 3.5 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was collected, dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound (12.5 mg, 42%). MS (ES): M / Ζ [M + H] = 501. ¹ H NMR: (400 MHz, chloroform-6): 1.90 (s, 3H), 4.82 (d, 1 = 14.3 Hz, 1H), 5.05 (d, 1 = 14.3 Hz , 1H), 7.14 (dd, 1 = 9.0, 1.6 Hz, 1H), 7.34 (d, 1 = 8.2 Hz, 2H), 7.50 (d, 1 = 8, 9 Hz, 1H), 7.63 (d, 1 = 0.9 Hz, 1H), 7.93 (d, 1 = 8.8 Hz, 2H) and 8.71 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-6): -58.1 (s, 3P).

Example 140. No. [2- (7-Bromo-6-chloro-2H-indazol-2-yl)] - 1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.043).

The title compound (5 mg, 17%) was also isolated from the same reaction mixture as described in Example 139. MS (ES): M / Ζ [M + H] = 501. Ί1 NMR: (400 MHz, chloroform-6): 1.99 (s, 3H),

4.87 (s, 2H), 7.22 (d, 1 = 8.8 Hz, 1H), 7.31 (d, 1 = 8.5 Hz, 2H), 7.63 (d, 1 = 8 9 Hz, 1H), 8.04 (d, 1 = 8.8 Hz, 2H), 8.31 (s, 1H) and 8.75 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-6): -58.1 (s, 3P).

Example 141. No. [1-Cyano-2- (3,6-dichloro-2H-indazol-2-yl)] - 1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.044).

A mixture of No. [2- (6-chloro-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (50 mg described in Example 132) and Ν-chlorosuccinimide (16 mg) in acetonitrile (1 ml) was heated to 60 ° C for 3.5 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was collected, dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound (46 mg, 85%). MS (ES): M / Ζ [M + H] = 457. ¹ H NMR: (400 MHz, chloroform-6): 1.92 (C, 3H), 4.80 (d, 1 = 14.3 Hz, 1H), 5.03 (d, 1 = 14.3 Hz , 1H), 7.15 (dd, 1 = 9.0, 1.4 Hz, 1H), 7.35 (d, 1 = 8.5 Hz, 2H), 7.57 (d, 1 = 9, 0 Hz, 1H), 7.63 (s, 1H), 7.93 (d, 1 = 8.7 Hz, 2H) and 8.65 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-6): -58.1 (s, 3P).

Example 142. Ν- [1-Cyano-2- (6,7-dichloro-2H-indazol-2-yl)] -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.045).

The title compound (6 mg, 11%) was also isolated from the same reaction mixture as described in Example 141. MS (ES): M / Ζ [M + H] = 457. Ί1 NMR: (400 MHz, chloroform-6): 1.99 (s, 3H),

4.87 (s, 2H), 7.22 (d, 1 = 8.8 Hz, 1H), 7.31 (d, 1 = 8.2 Hz, 2H), 7.59 (d, 1 = 8 9 Hz, 1H), 8.02 (d, 1 = 8.8 Hz, 2H), 8.26 (s, 1H) and 8.81 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-6): -58.1 (s, 3P).

Example 143. No. [1-Cyano-2- (3,7-dibromo-4,6-dichloro-2H-indazol-2-yl)] - 1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.046).

Mixture No. [2- (4,6-dichloro-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide described in Example 134 and an excess of Ν-bromosuccinimide in acetonitrile (1 ml) heated to 60 ° C. overnight. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was collected, dried over sodium sulfate, filtered and concentrated under reduced pressure.

- 66 016912 pressure to obtain the residue, which is purified by chromatography (81O ₂ , heptane / EA) to obtain the title compound (13 mg). MS (ES): M / Ζ [M + H] = 613. ¹ H NMR: (400 MHz, chloroform-ά): 1.97 (s, 3H), 4.75 (broad s, 1H), 4.88 (d, 1 = 14.3 Hz, 1H), 5, 14 (d, 1 = 14.3 Hz, 1H), 7.31 (d, 1 = 8.3 Hz, 2H), 8.05 (d, 1 = 8.8 Hz, 2H) and 8.65 ( s, 1H). ¹⁹ P NMR (376 MHz, chloroform-ά): -58.1 (s, 3P).

Example 144. No. [2- (7-Bromo-6,7-dichloro-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.047).

The title compound (18 mg) was also isolated from the same reaction mixture described in Example 143. MS (ES): M / Ζ [M + No.] = 557. Ή NMR: (400 MHz, chloroform-ά): 2.00 (s, 3H), 4.84-4.93 (m, 2H), 7.25 (s, 1H), 7.31 (d, 1 = 8.4 Hz, 2H), 8.02 (d, 1 = 8.8 Hz, 2H), 8.35 (s, 1H) and 8.57 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-ά): -58.1 (s, 3P).

The compound of example 145 receive according to the following General reaction scheme:

Example 145. Ν- | 2- (6-Chloro-3-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.050).

Using a procedure similar to that described in Example 1, except for the use of 2 amino-3- (6-chloro-3-methyl-2H-indazol-2-yl) -2-methylpropionitrile (33 mg), the title compound was isolated as a white solid substances (31 mg, 52%). Ή NMR: (400 MHz, chloroform-ά): 1.98 (s, 3H), 2.79 (s, 3H), 4.69 (d, 1H), 4.83 (d, 1H), 7, 05 (dd, 1 = 8.9, 1.6 Hz, 1H), 7.34 (d, 1 = 8.2 Hz, 2H), 7.55 (d, 1 = 9.0 Hz, 1H), 7.60 (d, 1 = 0.9 Hz, 1H), 7.96 (d, 1 = 8.8 Hz, 2H) and 9.19 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-ά): -58.1 (s, 3P).

2-amino-3- (6-chloro-3-methyl-2H-indazol-2-yl) -2-methylpropionitrile was prepared using the procedure similar to that described in example 1, part b, except for using 1- as the starting material. (6-chloro-3-methyl-2H-indazol-2-yl) propan-2-one. 1- (6-Chloro-3-methyl-2H-indazol-2yl) propan-2-one is obtained using a procedure similar to that described in Example 105, parts c and ά, except for using 2- [2- as the starting material (tert-butyldimethylsilanyloxy) propyl] -6-chloro-3-methyl-2H-indazole, which is prepared as follows.

a. To a solution of diisopropylamine (0.31 ml) in THF (3 ml) was added a solution of n-butyllithium (1.6 molar in hexane, 1.26 ml) at -78 ° C. After stirring for 30 minutes at −78 ° C., a solution of 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-3-methyl-2H-indazole (469 g) described in Example 132, part a, is added. in THF (3 ml) and the mixture was allowed to warm to -30 ° C for 1 h. Methyl iodide (0.126 ml) was added at -30 ° C and the mixture was allowed to warm to room temperature, then heated to 50 ° C for 24 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was collected, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue which was purified by chromatography (occupies 8 _2, heptane / EA) to give a mixture (1.3: 1, 408 mg) of the desired 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-3-methyl-2H-indazole and the starting material, 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-2H-indazole.

The compounds of examples 146-149 receive according to the following General reaction scheme:

Αεβΐοηιίπβ

ΟζΟΠΟίνδΙδ οχιΰβίινβ с1еауада

Асе Ош1п1е - acetonitrile

Οζοηο1ν $ ΐ8 og oh1daPue skauase - ozonolysis or oxidative breakdown

Ohsha Pop oxidation ог, OSM - or DIEA, DXM

Final product: ν = Ν; At CH; X = C-Kyu; Υ = € -Κ _η ;

- 67 016912

OS-1C; P = K;

K ₃ = K ₄ = H; a = 1; K ₅ = CH ₃ ; 1Κ..11;

Ζ = Ο (Ό); K ₇ = p-phenyl-K.

Example 146. No. [2- (6-Chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 3.001).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (15 mg) , the title compound is isolated as a white solid (24 mg, 82%). MS (ES): M / Ζ [M + H] = 454. ¹ H NMR: (400 MHz, chloroform): 1.91 (s, 3Η), 4.52 (d, 1 = 14.2 Hz, 1Η), 4.66 (s, 3Η), 4.85 (d, 1 = 14.2 Hz, 1Η), 7.33 (d, 1 = 8.2 Hz, 2H), 7.77 (d, 1 = 2.0 Hz, 1Η), 7.94 (d , 1 = 8.8 Hz, 2H), 8.31 (d, 1 = 2.0 Hz, 1Η) and 8.74 (s, 1H). ¹⁹ G NMR (376 MHz, chloroform): -58.1 (s, 3P).

2-amino-3- (6-chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (39 mg) was quantified using a procedure similar to that described in example 1 , part b, except for using 1- (6-chloro-3-methoxy-2H-pyrazolo [4,3b] pyridin-2-yl) propan-2-one (32 mg) as the starting material. 1- (6-Chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, part a-th, except using 5-chloro-3-nitropyridin-2-carboxyaldehyde (1.2 g) and decaborane in part a to produce 2- [2- (tert-butyldimethylsilanyloxy) propyl] - (5-chloro-3-nitropyridin-2-ylmethyl ) amine (0.4 g, 17%). 5 Chloro-3-nitropyridin-2-carboxyaldehyde is obtained using a procedure similar to that used in example 136, part a, except for using 2-amino6-chloro-3-nitropyridine as the starting material or using commercially available 2-bromo-5- chloro-3 nitropyridine in part b. As an alternative, oxidative cleavage is carried out using a 4% solution of osmium tetroxide in water (2 ml) and sodium periodate (1.2 g) in a mixture of THF and water (10: 1, 20 ml) in part c instead of ozonolysis, and then the procedure similar to that described in example 61 to obtain 5chloro-3-nitropyridin-2-carboxyaldehyde (0.72 g, 72%) from 5-chloro-3-nitro-2-vinylpyridine (1 g).

Example 147. No. [2- (6-Chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethylthiobenzamide (compound No. 3.002).

Using a procedure similar to that described in Example 1, except for using 2amino-3- (6-chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (15 mg, described in Example 146) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (20 mg, 67%). MS (ES): M / Ζ [M + H] = 470. ¹ H NMR: (400 MHz, chloroform): 1.92 (s, 3Η), 4.53 (d, 1 = 14.2 Hz, 1Η), 4.67 (s, 3Η), 4.86 (d, 1 = 14.2 Hz, 1Η), 7.77-7.82 (m, 3Η), 7.93 (d, 1 = 8.2 Hz, 2H), 8.31 (d, 1 = 1.9 Hz, 1H) and 8.82 (s, 1H). ¹⁹ G NMR (376 MHz, chloroform): -42.3 (s, 3G).

Example 148. No. [2- (6-Bromo-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide ( compound No. 3.007).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-bromo-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (20 mg), the title compound is isolated as a white solid (21 mg, 66%). ¹ Η NMR: (400 MHz, chloroform): 1.93 (s, 3Η), 2.57 (s, 3Η), 4.51 (d, 1 = 14.2 Hz, 1H), 4.66 (s, 3Η), 4.85 (d, 1 = 14.2 Hz, 1H), 7.31 (d, 1 = 8.3 Hz, 2H), 7.97 (d, 1 = 8.7 Hz , 2H), 8.39 (s, 1Η) and 9.03 (s, 1Η). ¹⁹ G NMR (376 MHz, chloroform): -58.1 (s, 3G).

2-amino-3- (6-bromo-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (20 mg) was obtained using a procedure similar to that described in example 1, part b, except for the use of 1- (6-bromo-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin2-yl) propan-2-one (117 mg). 1- (6-Bromo-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, part a- th, except for the use of 5-bromo-4-methyl-3-nitropyridin-2-carboxaldehyde (5.5 g) in part a to obtain [2 (tert-butyldimethylsilanyloxy) propyl] - (5-bromo-4-methyl- 3-nitropyridin-2-ylmethyl) amine (6 g, 67%). 5-Bromo-4-methyl-3-nitropyridin-2-carboxaldehyde is obtained using a procedure similar to that described in Example 136, part a-c, with the exception of using 2 amino-5-bromo-4-methyl-3- as the starting material nitropyridine (58.6 g) and the use of iodine (64 g) in part a instead of copper bromide to obtain 5-bromo-2-iodo-4-methyl-3-nitropyridine (28.7 g, 33%). Oxidative cleavage using a 4% solution of osmium tetroxide in water (3 ml) and sodium periodate (23.1 g) is carried out in a mixture of THF and water (10: 1, 330 ml) in part c instead of ozonolysis, and then a procedure similar to that described in example 61 to obtain 5-bromo-4-methyl-chloro-3-nitropyridine-2-carboxyaldehyde (11.7 g, 59%) from 5 bromo-4-methyl-3-nitro-2-vinylpyridine (18.8 g ) 2-amino-5-bromo-4-methyl-3-nitropyridine (120.2 g, 85%) was obtained using the procedure similar to that described in example 38, part a, except for using 2-amino-4 as the starting material methyl-3-nitropyridine (101.5 g).

Example 149. No. [2- (6-Chloro-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide ( compound No. 3.008).

Using a procedure similar to that described in Example 1, except for using 2amino-3- (6-chloro-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (28 mg)

- 68 016912 the title compound is isolated as a white solid (17 mg, 38%). ¹ H NMR: (400 MHz, chloroform-b): 1.93 (s, 3H), 2.56 (s, 3H), 4.51 (d, 1 = 14.2 Hz, 1H), 4.66 (s, 3H), 4.86 (d, 1 = 14.2 Hz, 1H), 7.31 (d, 1 = 8.4 Hz, 2H), 7.98 (d, 1 = 8.7 Hz , 2H), 8.28 (s, 1H) and 9.05 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-3- (6-chloro-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (26 mg) was obtained using a procedure similar to that described in example 1, part b, except for using 1- (6-chloro-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridine-

2-yl) propan-2-one (78 mg). 1- (6-Chloro-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, part a- b, with the exception of using 5-chloro-4-methyl-3-nitropyridin-2-carboxyaldehyde (1.3 g) in part a to obtain [2 (tert-butyldimethylsilanyloxy) propyl] - (5-chloro-4-methyl- 3-nitropyridin-2-ylmethyl) amine (1.4 g, 57%). 5-Chloro-4-methyl-3-nitropyridin-2-carboxyaldehyde is prepared using a procedure similar to that described in Example 136, part ac, except for using 2-amino-5-chloro-4-methyl- as the starting material. 3-nitropyridine (32 g), partially to form 2-bromo-5-chloro-4-methyl-

3-nitropyridine (25.2 g, 59%). Oxidative cleavage using a 4% solution of osmium tetroxide in water (1.5 ml) and sodium periodate (2.5 g) is carried out in a mixture of THF and water (10: 1, 60 ml) in part c instead of ozonolysis, and then the procedure, similar to that described in example 61 to obtain 5-chloro-4-methyl-3nitropyridin-2-carboxyaldehyde (1.3 g, 56%) from 5-chloro-4-methyl-3-nitro-2-vinylpyridine (2.3 g ) 2Amino-5-chloro-4-methyl-3-nitropyridine (4.6 g, 75%) was obtained using the procedure similar to that described in example 38, part a, except for using 2amino-4-methyl-3 as the starting material. -nitropyridine (5 g) and the use of Ν-chlorosuccinimide (5.8 g) instead of Ν bromosuccinimide.

The compounds of examples 150-152 obtained according to the following General reaction scheme:

to,

Ogopo1u215 og οχιάβΐινβ s1eachade

(ViOIO ^x '= ^νη 2 Ase1op1ych1e I

CuBr V OG I;

Manso ₃ hell ETOAS οί ΟΙΕΑ, OSM

Asexcpc - acetonitrile

Οζοηοίγβίβ og Ohmayue Skaua ^ e - ozonolysis or oxidative cleavage of OhShayop - oxidation of ca <, - cat.

ΟΙΕА, OSM - or DIEA, DXM

Final product:

ν = Ν; \\ 'C-11; X = C-Kyu; Y = CK _P ;

OS-K-; Ρ = Ν;

K ₃ = H4 = H; a = 1; K ₅ = CH ₃ ; 1C-11;

Ζ = ί '(Ο); K ₇ = p-phenyl-K.

Example 150. No. [2- (6-Bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 3.009).

Using a procedure similar to that described in Example 1, except for using 2amino-3- (6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (27 mg) , the title compound is isolated as a white solid (5 mg, 11%). MS (ES): M / Ζ [M + H] = 482. ¹ H NMR: (400 MHz, chloroform-b): 1.97 (s, 3H), 2.68 (s, 3H), 4.82 (d, 1H), 4.98 (d, 1H), 7 32 (d, 1 = 8.3 Hz, 2H), 7.93 (d, 1 = 8.7 Hz, 2H), 8.38 (s, 1H), 8.41 (s, 1H) and 8 61 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-3- (6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (33 mg) was obtained using a procedure similar to that described in example 1, part b, with the exception of using 1- (6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one (27 mg) as starting material. 1- (6-Bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, parts c and b, except using as starting material 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-bromo-7-methyl-2H-pyrazolo [4,3b] pyridine. 2- [2- (tert-Butyldimethylsilanyloxy) propyl] -6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridine (0.15 g, 9%) is isolated together with 1- (6-bromo -7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-ol (0.14 g, 12%) using a procedure similar to that described in example 132, part a, except using [2- (tert-butyldimethylsilanyloxy) propyl] - (5-bromo-4-methyl-3-nitropyridin-2-ylmethyl) amine (1.9 g) described in Example 148.

Example 151. No. [2- (6-Bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4

69 016912 trifluoromethylthiobenzamide (compound No. 3.023).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (56.7 mg described in Example 150) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (26 mg, 27%). MS (ES): M / Ζ [M + H] = 498. ¹ H NMR: (400 MHz, chloroform-b): 1.97 (s, 3H), 2.67 (s, 3H), 4.82 (d, 1H), 4.97 (d, 1H), 7 , 77 (d, 1 = 8.2 Hz, 2H), 7.92 (d, 1 = 8.3 Hz, 2H), 8.38 (s, 1H), 8.54 (s, 1H) and 8 61 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -42.3 (s, 3P).

Example 152. N- [2- (6-Chloro-7-methyl-2Η-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethoxybenzamide (compound No. 3.010).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-chloro-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (32 mg) , the title compound is isolated as a white solid (4 mg, 9%). ¹ H NMR: (400 MHz, chloroform-b): 1.97 (s, 3H), 2.67 (s, 3H), 4.83 (d, 1H), 4.97 (d, 1H), 7 32 (d, 1 = 8.2 Hz, 2H), 7.93 (d, 1 = 8.7 Hz, 2H), 8.39 (s, 1H), 8.44 (s 1H) and 8, 51 (s, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-3- (6-chloro-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (33 mg) was obtained using a procedure similar to that described in example 1, part b, with the exception of using 1- (6-chloro-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one (35 mg) as starting material. 1- (6-Chloro-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, parts c and b, except using as starting material 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-7-methyl-2H-pyrazolo [4,3b] pyridine. 2- [2- (tert-Butyldimethylsilanyloxy) propyl] -6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridine (0.13 g, 13%) is isolated together with 1- (6-chloro -7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-ol (0.13 mg, 21%) using a procedure similar to that described in example 132, part a, except the use of [2- (tert-butyldimethylsilanyloxy) propyl] - (5-chloro-4-methyl-3-nitropyridin-2-ylmethyl) amine (1.1 g) described in Example 149.

The compounds of examples 153-154 obtained according to the following General reaction scheme:

Final product:

ν = Ν; A = CH; X = CK ₁₀ ; Υ = σ &_η;

Ο = Ρ = Ν;

K ₃ = Cd = H; a = 1; K ₅ = CH ₃ ; K.11;

7 = C (O); K ₇ = p-phenyl-K.

Example 153. N- [2- (6-Bromo-7-methyl-2Η- [1,2,3] triazolo [4,5-b] pyridin-2-yl) -1-cyano-1-methylethyl] - 4 trifluoromethoxybenzamide (compound No. 3.003).

When using a procedure similar to that described in example 1, except for the use of 2 amino-3- (6-bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridin-2-yl) - 2-methylpropionitrile (60 mg), the title compound is isolated as a white solid (60 mg, 61%). CT = 0.4 (1: 1 EA / heptane). MS (ES): M / Ζ [M-H] = 481. Ή NMR: (400 MHz, DMSO-b ₆ ): 1.76 (s, 3H), 2.56 (s, 3H), 5.41 (d, 1H), 5.54 (d, 1H), 7 52 (d, 1 = 8.2 Hz, 2H), 7.92 (d, 1 = 8.6 Hz, 2H) and 8.85 (s, 2H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -57.1 (s, 3P).

2-amino-3- (6-bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridin-2-yl) -2-methylpropionitrile (0.15 g, 55% ) are obtained using a procedure similar to that described in Example 1, part b, except for using 1- (6-bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] as the starting material pyridin-2yl) propan-2-one (0.25 g), which is prepared as follows.

a. To a mixture of 2-methyl-2-propen-1-ol (1.4 ml) and triphenylphosphine (3.7 g) in THF (80 ml), diisopropylazodicarboxylate (Ό ^ Ό, 2.7 ml) was added dropwise. After stirring for 15 minutes, 6-bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridine (2.3 g) was added and the reaction was stirred for 3 hours at room temperature. The mixture was poured into water, extracted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (81O ₂ , heptane / EA) to obtain 6-bromo-7-methyl2- (2-methylallyl) -2H- [1,2 , 3] triazolo [4,5-b] pyridine. 6-Bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridine (2.4 g, 74%) was obtained using a procedure similar to that described in example 13, part a, for is

- 70 016912 by using 5-bromo-4-methylpyridin-2,3-diamine (3.5 g, 80%) as the starting material, which was obtained using a procedure similar to that described in Example 38, part b, except for using as starting material, 2-amino-5-bromo-4-methyl-3-nitropyrine (5 g) described in Example 148.

B. To a solution of 6-bromo-7-methyl-2- (2-methylallyl) -2H- [1,2,3] triazolo [4,5-b] pyridine (0.9 g) in a mixture of THF and water (8: 1, 18 ml) sodium periodate (2 g) and a 4% solution of osmium tetroxide in water (2 ml, 5 mol%) are added. After stirring overnight at room temperature, the mixture was quenched with 10% sodium thiosulfate solution, extracted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (31O ₂ , heptane / EA) to obtain 1- (6-bromo-7-methyl-2H [1,2,3] triazolo [4,5-b] pyridin-2-yl) propan-2-one (0.3 g, 33%).

Example 154. No. [2- (6-Bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4 trifluoromethylthiobenzamide (compound No. 3.004).

When using a procedure similar to that described in example 1, except for the use of 2 amino-3- (6-bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridin-2-yl) - 2-methylpropionitrile (90 mg, described in Example 153) and 4-trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid (65 mg, 43%). VH = 0.4 (1: 1 EA / heptane). MS (ES): M / Ζ [M-H] = 497. ¹ H NMR: (400 MHz, DMSO-b6): 1.76 (s, 3H), 2.56 (s, 3H), 5.40 (d, 1H), 5.54 (d, 1H), 7 82-7.94 (m, 4H), 8.86 (s, 1H) and 8.93 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -42.0 (s, 3P).

The compounds of examples 155-158 obtained according to the following General reaction scheme:

Αοβίοηΐίπΐε - OhShayop acetonitrile - oxidation - aq.

from ОС, OSM - or DIEA, DXM

Final product:

ν = Ν; At CH; X = CB ₁₀ ; Y = CB ₁₁ ;

S-11; ₽ = Ν;

B ₃ = B ₄ = H; a = 1; B ₅ = CH ₃ ; N ... N;

7 = C (O); B ₇ = p-phenyl-B.

Example 155. No. [2- (6-Chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.005).

Using a procedure similar to that described in Example 1, except for using 2amino-3- (6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (1.1 g), the compound was isolated as a white solid (1 g, 49%). MS (ES): M / Ζ [M + H] = 424. ¹ H NMR: (400 MHz, chloroform-b): 1.95 (s, 3H), 4.86 (d, 1 = 14.0 Hz, 1H), 5.02 (d, 1 = 14.0 Hz , 1H), 7.33 (d, 1 = 8.1 Hz, 2H), 7.88 (d, 1 = 8.7 Hz, 2H), 8.02 (dd, 1 = 2.1, 0, 9 Hz, 1H), 8.03 (s, 1H), 8.42 (d, 1 = 0.8 Hz, 1H) and 8.55 (d, 1 = 2.1 Hz, 1H). ¹⁹ P NMR (376 MHz, chloroform-b): -58.1 (s, 3P).

2-amino-3- (6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (1.1 g, 97%) was obtained using a procedure similar to that described in example 1 , part b, with the exception of using 1- (6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one (1 g) as starting material. 1- (6-Chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one is obtained using a procedure similar to that described in example 105, parts c and b, except for use in as the starting material, 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-2H-pyrazolo [4,3-b] pyridine, which is prepared as follows.

a. To a solution of 5-chloro-3-nitropyridin-2-carboxaldehyde (1 g) described in Example 146 in 1,2-dichloroethane (20 ml) was added molecular sieve powder (4 A) and 2- (tert-butyldimethylsilanyloxy) propylamine (1 , 22 g) described in example 105, part a. After stirring overnight at room temperature, sodium cyanoborohydride (0.4 g) and acetic acid (0.33 ml) were added at 0 ° C. After stirring for 1 h at 0 ° C., the reaction mixture was heated at 65 ° C. overnight. The reaction mixture was filtered through a Ce1be® layer and concentrated under reduced pressure to obtain a residue, which was purified by chromatography (31O ₂ , heptane / EA) to obtain 2- [2- (tert-butyldimethylsilanyloxy) propyl] -6-chloro-2H-pyrazolo [4, 3-b] pyridine (0.6 g, 37%). MS (ES): M / Ζ

71 016912 [M + H] = 326. ^! H NMR: (400 MHz, chloroform-ά): -0.37 (s, 3H), -0.09 (s, 3H), 0.79 (s, 9H), 1.24 (d, 1 = 6 , 1 Hz, 3H), 4.21-4.31 (m, 1H), 4.33-4.38 (m, 1H), 4.40-4.47 (m, 1H), 8.00 ( dd, 1 = 2.1, 0.9 Hz, 1H), 8.22 (d, 1 = 0.7 Hz, 1H) and 8.48 (d, 1 = 2.1 Hz, 1H).

Example 156. No. [2- (6-Chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 3.006).

Using a procedure similar to that described in example 1, except for the use of 2amino-3- (6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (35 mg, described in example 155 ) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (13 mg, 20%). MS (ES): M / Ζ [M + H] = 440. Ή NMR: (400 MHz, chloroform-ά): 1.96 (s, 3H), 4.86 (d, 1 = 14.0 Hz, 1H), 5.01 (d, 1 = 14.0 Hz, 1H), 7.71-7.83 (m, 2H), 7.83-7.92 (m, 2H), 8.02 (dd, 1 = 2.1, 0.9 Hz, 1H), 8 12 (s, 1H), 8.43 (d, 1 = 0.7 Hz, 1H) and 8.56 (d, 1 = 2.1 Hz, 1H). ¹⁹ E NMR (376 MHz, chloroform-ά): -42.2 (s, 3E).

Example 157. No. [2- (6-Bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.011).

Using a procedure similar to that described in Example 1, except for the use of 2amino-3- (6-bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (156 mg), the title compound was isolated as a white solid (133 mg, 48%). MS (ES): M / Ζ [M + H] = 468. ¹ H NMR: (400 MHz, chloroform-ά): 1.93 (s, 3H), 4.84 (d, 1 = 14.0 Hz, 1H), 5.00 (d, 1 = 14.1 Hz , 1H), 7.31 (d, 1 = 8.1 Hz, 2H), 7.82-7.90 (m, 2H), 7.99 (s, 1H), 8.20 (dd, 1 = 1.9, 0.8 Hz, 1H), 8.39 (s, 1H) and 8.61 (d, 1 = 2.0 Hz, 1H). ¹⁹ E NMR (376 MHz, chloroform-ά): -58.1 (s, 3E).

2-amino-3- (6-bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (416 mg 80%) was obtained using the procedure similar to that described in example 1, part b , with the exception of using 1- (6-bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one (471 mg) as starting material. 1- (6Bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) propan-2-one is obtained using a procedure similar to that described in Example 105, parts c and ά, except for using as starting material 2 [2- (tert-butyldimethylsilanyloxy) propyl] -6-bromo-2H-pyrazolo [4,3-b] pyridine (289 mg, 39%), which was obtained using a procedure similar to that described in example 155, except for use in as the starting material, 5-bromo-3-nitropyridin-2-carboxyaldehyde (462 mg). 5-Bromo-3nitropyridin-2-carboxyaldehyde is obtained using a procedure similar to that described in Example 136, part ac, with the exception of using 2-amino-5-bromo-3nitropyridine (50 g) and iodine (69) , 9 g) in part a, instead of copper bromide, to obtain 5-bromo-2-iodo-3-nitropyridine as a yellow solid (27.4 g, 36%) Oxidative cleavage using a 4% solution of osmium tetroxide in water (4 ml) and sodium periodate (6.7 g) is carried out in a mixture of THF and water (10: 1, 390 ml) in part c instead of ozonolysis, and then the procedure under as described in Example 61 to obtain 5-bromo-3-nitropyridin-2-carboxyaldehyde as a tan solid (3.8 g, 62%) from 5-bromo-3-nitro-2-vinylpyridine (6 g) .

Example 158. No. [2- (6-Bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 3.012).

When using a procedure similar to that described in example 1, except for the use of 2amino-3- (6-bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) -2-methylpropionitrile (223 mg described in example 157 ) and 4-trifluoromethylthiobenzoyl chloride, the title compound is isolated as a white solid (145 mg, 38%). MS (ES): M / Ζ [M + H] = 484. ^! H NMR: (400 MHz, chloroform-ά): 1.95 (s, 3H), 4.86 (d, 1 = 14.0 Hz, 1H), 5.01 (d, 1 = 14.1 Hz, 1H), 7.78 (d, 1 = 8.3 Hz), 7.78 (d, 1 = 8.3 Hz, 2H), 7.84-7.90 (m, 2H), 8.11 ( s, 1H), 8.22 (dd, 1 = 2.0, 1.0 Hz, 1H), 8.42 (d, 1 = 0.8 Hz, 1H) and 8.64 (d, 1 = 2 , 0 Hz, 1H). ¹⁹ G NMR (376 MHz, chloroform-ά): -42.2 (s, 3P).

The compounds of examples 159, 160 were prepared according to the following general reaction scheme:

Final product:

V = N; ν ^ Ή; X = C-K1ο; Υ = € -Κ _η ;

OS-K-; P = K;

K ₃ = K ₄ = H; a = 1; K ₅ = CH ₃ ; K ₆ = H;

7 = C (O); K ₇ = p-phenyl-K.

Example 159. Ν- [1-Cyano-2- (3,6-dichloro-2H-pyrazolo [4,3-6] pyridin-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.017).

Mixture No. [2- (6-Chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (134 mg described in example 155) and Ν -chlorosuccinimide (51 mg) in acetonitrile (3.5 ml) per

- 72 016912 heated at 60 ° C during the night. The mixture was concentrated under reduced pressure to give a residue, which was purified by chromatography (81O ₂ , heptane / EA) to give the title compound as a white solid (129 mg, 89%). MS (ES): M / Ζ [M + H] = 458. ^! H NMR: (400 MHz, DMSO-b6): 1.78 (s, 3H), 5.10-5.20 (m, 2H), 7.53 (d, 1 = 8.3 Hz, 2H), 7.97 (d, 1 = 8.8 Hz, 2H), 8.43 (d, 1 = 2.0 Hz, 1H), 8.59 (d, 1 = 2.0 Hz, 1H) and 8, 99 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b6): -57.1 (s, 3P).

Example 160. M- [2- (3-Bromo-6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.019 )

A mixture of L- [2- (6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (134 mg described in Example 155) and Ν-bromosuccinimide (68 mg) in acetonitrile (3.5 ml) was heated at 60 ° C. overnight. The mixture was concentrated under reduced pressure to give a residue, which was purified by chromatography (81O ₂ , heptane / EA) to give the title compound as a white solid (125 mg, 80%). MS (ES): M / Ζ [M + H] = 502. Ί1 NMR: (400 MHz, DMSO-b ₆ ): 1.78 (s, 3H), 5.10-5.22 (m, 2H), 7.52 (d, 1 = 8.2 Hz, 2H) , 7.98 (d, 1 = 8.7 Hz, 2H), 8.43 (d, 1 = 2.0 Hz, 1H), 8.58 (d, 1 = 1.9 Hz, 1H) and 9 , 00 (s, 1H). ¹⁹ P NMR (376 MHz, DMSO-b ₆ ): -57.1 (s, 3P).

Table 1

ν = ^ Β8; ν = € -Β9; X = C-Kyu; Υ = € -Β _π ;

Ο = Ρ = Ν;

K3 = K4 = K6 = H; a = 1; K5 = CH3;

Ζ = Ο (Ό); K ₇ = p-phenyl-K

Compound in to. Kth % 1.001 OCP ₃ Me n C1 n n 1.002 SRz Me n C1 n n 1.003 8CP ₃ Me n C1 n n 1.004 OCP Me n n n n 1.005 8CP ₃ Me n n n n 1.006 OCP Me n Me n n 1.007 8CP ₃ Me n Me n n 1.008 OCP ₃ Me n SR n n 1.009 8CP ₃ Me and SR n n 1.010 OSRz Me n C1 C1 n 1.011 8CP ₃ Me n C1 C1 and 1.012 OCP ₃ Me C1 n C1 n 1.013 8CP ₃ Me C1 n C1 n 1.014 OCP ₃ Me C1 n SR n 1.015 8CP ₃ Me C1 n SRz n 1.016 OCP ₃ Me and sy n n 1.017 8СР, Me n SI n n 1.018 OCP ₃ Me SRz n SRz n 1.019 8CP ₃ Me SRz n SR and 1.020 OCP ₃ Me n Vg n and 1.021 8CP ₃ Me n Vg n n 1.022 8 OSR ₃ Me n SI n n 1.023 5 OSR ₃ Me C1 n SR n 1.024 KOSRz Me C1 n C1 n 1.025 8О ₂ СР ₃ Me C1 n C1 n 1.026 5О ₂ Срз Me n SRz n n 1.027 8О ₂ Срз Me n ΌΝ n n 1.028 8О ₂ СР ₃ Me C1 n SR n 1.029 8О ₂ Срз Me n n N and 1.030 8О ₂ Срз Me n Me n n 1.031 8О ₂ СР ₃ Me n C1 n and 1.032 OP11 Me n C1 n n

- 73 016912

1.033 OSRz Me Me n C1 n 1.034 8CP ₃ Me Me n C1 n 1.035 OCP ₃ Me N OSRz n n 1.036 8CP ₃ Me n OCP ₃ n n 1.037 OCP ₃ Me SRz n C1 n 1,038 8CP ₃ Me SRz n C1 n 1.039 OR Me Me n C1 n 1.040 OSRz Me N C1 Me n 1.041 8CP ₃ Me n C1 Me n 1.042 OR Me SRz n C1 n 1.043 OSRz Me C1 n n n 1.044 8CP ₃ Me C1 n n and 1.045 OR Me C1 n n n 1.046 Pb Me C1 n C1 n 1.047 OSRz Εΐ n C1 n n 1.048 8CP ₃ Εΐ n C1 n n 1.049 OSRz CH ₂ CH (CH ₃ ) ₂ n C1 n n 1,050 8CP ₃ CH ₂ CH (CH ₃ ) ₂ n C1 n n 1.051 OSRz tert vi n C1 n n 1.052 8CP ₃ tert vi n C1 n n 1.053 1-Vi Me C1 n C1 n 1.054 OSRz Me 0Ν n SRz n 1.055 8CP ₃ Me 0Ν n SRz n 1.056 OSRz Me SRz n ΟΝ n 1.057 OSRz Me Vg C1 n n 1.058 OCP ₃ CH ₂ OH n C1 n m 1.059 8CP ₃ CH ₂ OH n C1 n n 1.060 OSRz Me Vg n C1 n 1.061 OSRz CH ₂ 8Me N C1 n n 1.062 OSRz CH ₂ OMe n C1 n n 1.063 OSRz СНО8О ₂ Me n C1 n n 1.064 OSRz Me C1 C1 n C1 1.065 8CP ₃ Me C1 C1 n C1 1.066 8CP ₃ Me SRz n SI n 1.067 OSG ₃ Me 0Ν n C1 n 1.068 OSG ₃ Me r-pb-srz n C1 n 1.069 SRRS Me C1 C1 n C1 1.070 OSRz Me C1 n OMe n 1.071 8CP ₃ Me C1 n OMe n 1.072 OSRz Me n OMe N n 1.073 8CP ₃ Me n OMe n n 1.074 OSRz Me ΟΗ ₂ ΝΗ ₂ n C1 n 1.075 OCP ₃ Me Vinyl n C1 n 1.076 8CP ₃ Me Vinyl n C1 n 1.077 OSRz Me CH (OH) CH ₂ OH n C1 n 1.078 OSRz Me CH (P) CH ₂ G n C1 n 1.079 OSRz Me Formil n C1 n 1.080 OSRz Me SLMmez n C1 n 1.081 OCP ₃ Me CH ₂ OH n C1 n 1.082 OCP ₃ Me CO ₂ N n C1 n 1.083 OSRz Me Vg C1 n Vg 1.084 OSRz Me СО ₂ Me n C1 N 1,085 8CE ₃ Me Vg C1 n Vg 1,086 OSRz Me Vg C1 n C1 1.087 8CP ₃ Me Vg C1 n C1 1.088 OSRz Me Vg C1 Vg C1 1,089 8CP ₃ Me Vg C1 Vg C1 1.090 OSRz Me R C1 n C1 1,091 8СГз Me R C1 n C1 1.092 OSRz Me Me C1 n Me 1.093 8СРз Me Me C1 n Me 1.094 OSRz Me R Vg n Me 1.095 8SG ₃ Me R Vg n Me

Compounds of general formula (1c) that are of particular interest:

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.001);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylbenzamide (compound No. 1.002;

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.003);

No. [2- (2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.004);

No. [2- (2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.005);

No. [1-cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.006);

No. [1-cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.007);

- 74 016912 No. [1-cyano-1-methyl-2- (5-trifluoromethyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.008);

No. [1-cyano-1-methyl-2- (5-trifluoromethyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.009);

N- [1-cyano-2- (5,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.010);

N- [1-cyano-2- (5,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.011);

N- [1-cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.012);

N- [1-cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.013);

No. [2- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.014);

No. [2- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.015);

No. [1-cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.016);

No. [1-cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.017);

No. [2- (4,6-bis- (trifluoromethyl) -2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.018);

No. [2- (4,6-bis- (trifluoromethyl) -2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.019);

No. [2- (5-bromo-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.020);

No. [2- (5-bromo-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.021);

No. [1-cyano-2- (5-cyano-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylsulfinyl benzamide (compound No. 1.022);

No. [2- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylsulfinylbenzamide (compound No. 1.023);

N- [1-cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylsulfinyl benzamide (compound No. 1.024);

N- [1-cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.025);

No. [1-cyano-1-methyl-2- (5-trifluoromethyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.026);

No. [1-cyano-1-methyl-2- (5-cyano-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.027);

No. [2- (4-chloro-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.028);

No. [2- (2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.029);

No. [1-cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.030);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylsulfonylbenzamide (compound No. 1.031);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-phenoxybenzamide (compound No.

1.032);

No. [2- (6-chloro-4-methyl-2H-benzotriazole-2-yl) - 1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.033);

No. [2- (5-chloro-4-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.034);

No. [1-cyano-1-methyl-2- (5-trifluoromethoxy-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.035);

No. [1-cyano-1-methyl-2- (5-trifluoromethoxy-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.036);

No. [2- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.037);

No. [2- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.038);

75 016912 No. [2- (6-chloro-4-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-phenoxybenzamide (compound No. 1.039);

No. [2- (5-chloro-6-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.040);

No. [1-cyano-1-methyl-2- (5-methyl-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.041);

No. [2- (6-chloro-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-phenoxybenzamide (compound No. 1.042);

No. [2- (4-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.043);

No. [2- (4-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.044);

No. [2- (4-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-phenoxybenzamide (compound No.

1.045);

No. [1-cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] biphenyl-4-carboxamide (compound No. 1.046);

No. {1 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -1-cyanopropyl} -4-trifluoromethoxybenzamide (compound No. 1.047);

No. {1 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -1-cyanopropyl} -4-trifluoromethylthiobenzamide (compound No. 1.048);

No. {1 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-3-methylbutyl} -4-trifluoromethoxybenzamide (compound No. 1.049);

No. {1 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-3-methylbutyl} -4-trifluoromethylthiobenzamide (compound No. 1.050);

No. {1 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-2,2-dimethylpropyl} -4-trifluoromethylthiobenzamide (compound No. 1.051);

No. {1 - [(5-chloro-2H-benzotriazol-2-yl) methyl] -1-cyano-2,2-dimethylpropyl} -4-trifluoromethylthiobenzamide (compound No. 1.052);

N- [1-cyano-2- (4,6-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-tert-butylbenzamide (compound No. 1.053);

No. [1-cyano-2- (4-cyano-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.054);

No. [1-cyano-2- (4-cyano-6-trifluoromethyl-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.055);

No. [1-cyano-2- (6-cyano-4-trifluoromethyl-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.056);

No. [2- (4-bromo-5-chloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.057);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1- (hydroxymethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.058);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1- (hydroxymethyl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.059);

No. [2- (4-bromo-6-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.060);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1- (methylthiomethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.061);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1- (methoxymethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.062);

No. [2- (5-chloro-2H-benzotriazol-2-yl) -1-cyano-1- (methanesulfonylmethyl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.063);

No. [1-cyano-1-methyl-2- (4,5,7-trichloro-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 1.064);

No. [1-cyano-1-methyl-2- (4,5,7-trichloro-2H-benzotriazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 1.065);

No. [1-cyano-2- (6-cyano-4-trifluoromethyl-2H-benzotriazol-2-yl) methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.066);

No. [2- (6-chloro-4-cyano-2H-benzotriazole-2-yl) - 1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.067);

No. {2- [6-chloro-4- (4-trifluoromethylphenyl) -2H-benzotriazol-2-yl] -1-cyano-1-methylethyl} -4-trifluoromethoxybenzamide (compound No. 1.068);

No. [1-cyano-1-methyl-2- (4,5,7-trichloro-2H-benzotriazol-2-yl) ethyl] -4- (1,2,2,2-tetrafluoroethyl) benzamide (compound No. 1.069 );

76 016912 No. [2- (4-chloro-6-methoxy-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.070);

No. [2- (4-chloro-6-methoxy-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.071);

N- [1-cyano-2- (5-methoxy-2H-benzotriazol-2-yl) - 1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.072);

N- [1-cyano-2- (5-methoxy-2H-benzotriazol-2-yl) - 1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.073);

No. [2- (4-aminomethyl-6-chloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.074);

No. [2- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.075);

No. [2- (6-chloro-4-vinyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.076);

No. {2- [6-chloro-4- (1,2-dihydroxyethyl) -2H-benzotriazol-2-yl] -1-cyano-1-methylethyl} -4-trifluoromethoxybenzamide (compound No. 1.077);

No. {2- [6-chloro-4- (1,2-difluoroethyl) -2H-benzotriazol-2-yl] -1-cyano-1-methylethyl} -4-trifluoromethoxybenzamide (compound No. 1.078);

No. {2- [6-chloro-4-formyl-2H-benzotriazol-2-yl] -1-cyano-1-methylethyl} -4-trifluoromethoxybenzamide (compound No. 1.079);

No. 2- [6-chloro-4-dimethylaminomethyl-2H-benzotriazol-2-yl-1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.080);

No. 2- [6-chloro-4-hydroxymethyl-2H-benzotriazol-2-yl] -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.081);

6-chloro-2- [2-cyano-2 - ({[[4- (trifluoromethoxy) phenyl] carbonyl} amino) propyl] -2H-benzotriazole-4-carboxylic acid (compound No. 1.082);

6-chloro-2- [2-cyano-2 - ({[((4-trifluoromethoxy) phenyl] carbonyl} amino) propyl] -2Nbenzotriazole-4-carboxylic acid methyl ester (compound No. 1.084);

No. [2- (5-chloro-4,7-dibromo-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.085);

No. [2- (4-bromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.086);

No. [2- (4-bromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.087);

No. [1-cyano-2- (4,6-dibromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.088);

No. [1-cyano-2- (4,6-dibromo-5,7-dichloro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.089);

N- [1-cyano-2- (4,6-dibromo-4-fluoro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.090);

No. [1-cyano-2- (5,7-dichloro-4-fluoro-2H-benzotriazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.091);

No. [2- (5-chloro-4,7-dimethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.092);

No. [2- (5-chloro-4,7-dimethyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.093);

No. [2- (5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 1.094);

No. [2- (5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 1.095).

Numbers 1.001-1.095 refer to the above compounds for identification and reference below.

- 77 016912

ν = ^; No. CB ,; X = C-Vu; Υ ^^;

OS-B-; P = K;

B3 = B ₄ = B _b = H; a = 1; B. C1B;

Ζ = Ο (Ό); B ₇ = p-phenyl-B

Compound # IN. to ₂ K ₈ to, In Kn 2.001 OCP ₃ N n νο ₂ n n 2.002 8СРз n n νο ₂ n n 2.003 OCP ₃ n n C1 n C1 2.004 OR n n C1 n C1 2.005 8CP ₃ n n C1 n C1 2.006 OSRz n n C1 n Me 2.007 8CP ₃ n n C1 n Me 2.008 OCP ₃ OMe n n C1 N 2.009 ZSRz OMe n n C1 N 2.010 OSRz Me n C1 n C1 2.011 8CP ₃ Me n C1 n C1 2.012 OCP ₃ OMe n C1 n n 2.013 8CP ₃ OMe n C1 n n 2.014 OSRz OE1 n C1 n n 2.015 8CP ₃ ΟΕΐ n C1 n n 2.016 OSRz OMe n n n n 2.017 OSRz O (CH ₂ ) ₂ OMe n n C1 n 2.018 OSRz Ο (ΟΗ ₂ ) ₂ ΝΜβ ₂ n n C1 n 2.019 8CP ₃ OMe n C1 n C1 2.020 OSRz OMe n C1 n C1 2.021 OCP ₃ OMe C1 n C1 n 2.022 8CP ₃ OMe C1 n C1 n 2.023 OSRz OMe n n Vg n 2.024 8CP ₃ OMe n n Vg n 2.025 OSRz OMe n n SR ₃ n 2.026 8СРз OMe n n SR ₃ n 2.027 OSRz OE1 n n C1 n 2.028 8CP ₃ OE " n and FROM! n 2.029 OCP ₃ O-p-rg n n C1 n 2.030 8CP ₃ O-p-rg n n C1 n 2.031 OSRz Oh p n n C1 n 2.032 OSRz OMe n n СО ₂ Me n 2.033 OSRz OMe n n ΝΟ ₂ n 2.034 OCP ₃ OMe n n νη ₂ n 2.035 OSRz OMe n n ΝΗΑε n 2.036 OSRz OMe n n οονη ₂ n 2.037 OSRz N n n C1 n 2.038 8CP ₃ N n n FROM! n 2.039 OSRz C1 n n C1 C1 2.040 OSRz n C1 n C1 n 2.041 8CE ₃ n C1 n C1 n 2.042 OSRz Vg and n C1 n 2.043 OSRz N n n C1 Vg

2.044 OSES C1 N n C1 and 2.045 OSRz n AND n C1 C1 2.046 OSRz Vg C1 n C1 Vg 2,047 OSRz n C1 n C1 Vg 2.048 OSRz n C1 n C1 C1 2.049 8CP ₃ and C1 n C1 C1 2.050 OSRz Me n n C1 n

Compounds of general formula (1b) that are of particular interest:

No. [1-cyano-1-methyl-2- (5-nitro-2H-indazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 2.001);

No. [1-cyano-1-methyl-2- (5-nitro-2H-indazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 2.002);

No. [1-cyano-2- (5,7-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.003);

No. [1-cyano-2- (5,7-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-phenoxybenzamide (compound No.

2.004);

No. [1-cyano-2- (5,7-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.005);

78 016912 No. [2- (5-chloro-7-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.006);

No. [2- (5-chloro-7-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.007);

No. [2- (6-chloro-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.008);

No. [2- (6-chloro-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.009);

N- [1-cyano-2- (5,7-dichloro-3-methyl-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.010);

No. [2- (5,7-dichloro-3-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.011);

No. [2- (5-chloro-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.012);

No. [2- (5-chloro-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.013);

No. [2- (5-chloro-3-ethoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.014);

No. [2- (5-chloro-3-ethoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.015);

N- [1-cyano-2- (3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.016);

No. {2- [6-chloro-3 - (2-methoxyethoxy) -2H-indazol-2-yl)] -1-cyano-1-methylethyl} -4-trifluoromethoxybenzamide (compound No. 2.017);

No. {2- [6-chloro-3 - (2-dimethylaminoethoxy) -2H-indazol-2-yl)] -1-cyano-1-methylethyl} -4-trifluoromethoxybenzamide (compound No. 2.018);

N- [1-cyano-2- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.019);

N- [1-cyano-2- (5,7-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.020);

N- [1-cyano-2- (4,6-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.021);

N- [1-cyano-2- (4,6-dichloro-3-methoxy-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.022);

No. [2- (6-bromo-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.023);

No. [2- (6-bromo-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.024);

N- [1-cyano-2- (3-methoxy-6-trifluoromethyl-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.025);

N- [1-cyano-2- (3-methoxy-6-trifluoromethyl-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.026);

No. [2- (6-chloro-3-ethoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.027);

No. [2- (6-chloro-3-ethoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.028);

No. [2- (6-chloro-3-propoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.029);

No. [2- (6-chloro-3-propoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.030);

No. [2- (6-chloro-3-butoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.031);

2- [2-cyano-2-methyl-2- (4-trifluoromethoxybenzoylamino) ethyl] -3-methoxy-2-indindazole-6-carboxylic acid methyl ester (compound No. 2.032) No. [1-cyano-2- (3-methoxy -6-nitro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.033);

No. [2- (6-amino-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.034);

No. [2- (6-acetylamino-3-methoxy-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.035);

methyl 2- [2-cyano-2-methyl-2- (4-trifluoromethoxybenoylzamino) ethyl] -3-methoxy-2H-indazole-6-carboxamide (compound No. 2.036);

- 79 016912

N- [2- (6-chloro-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.037);

N- [2- (6-chloro-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.038);

N- [1-cyano-1-methyl-2- (3,6,7-trichloro-2Η-indazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 2.039);

N- [1-cyano-2- (4,6-dichloro-2Η-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.040);

N- [1-cyano-2- (4,6-dichloro-2Η-indazol-2-yl) -1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 2.041);

N- [2- (3-bromo-6-chloro-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.042);

N- [2- (7-bromo-6-chloro-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.043);

Ν- [1-cyano-2- (3,6-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.044);

N- [1-cyano-2- (6,7-dichloro-2Η-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.045);

Ν- [1-cyano-2- (3,7-dibromo-4,6-dichloro-2H-indazol-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.046);

N- [2- (7-bromo-6,7-dichloro-2Η-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.047);

N- [1-cyano-1-methyl-2- (4,6,7-trichloro-2Η-indazol-2-yl) ethyl] -4-trifluoromethoxybenzamide (compound No. 2.048);

N- [1-cyano-1-methyl-2- (4,6,7-trichloro-2Η-indazol-2-yl) ethyl] -4-trifluoromethylthiobenzamide (compound No. 2.049);

No. [2- (6-chloro-3-methyl-2H-indazol-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 2.050).

2.001-2.050 refer to the above compounds for identification and reference below.

Table 3

ν = Ν; A = CK ₉ ; X = CK ₁₀ ; Υ ^ - ^;

OS-K, Ρ = Ν;

K ₃ = K ₄ = K ₆ = H; a = 1; K ₅ = CH ₃ ; 7 = C (O); K ₇ = p-phenyl-K

Compound to 0 CL> Kth K11 3.001 OCP ₃ S-OMe n C1 n 3.002 8CP ₃ S-OMe n C1 n 3.003 OCP ₃ N n Vg Me 3.004 8CP ₃ N n Vg Me 3.005 OCP ₃ CH n C1 N 3.006 8СР; CH n C1 N 3.007 OCP ₃ S-OMe n Vg Me 3.008 OCP ₃ S-OMe n C1 Me 3.009 OCP ₃ CH n Vg Me 3.010 OCP ₃ CH n C1 Me 3.011 OCP ₃ CH n Vg n 3.012 8CP ₃ CH n Vg n 3.013 OCP ₃ CH n C1 FROM! 3.014 8CP ₃ CH n C1 C1 3.015 OCP ₃ CH n Vg FROM! 3.016 8CP ₃ CH n Vg C1 3.017 OCP ₃ C-C1 n C1 n 3.018 8CP ₃ C-C1 n C1 n 3.019 OCP ₃ S-Vg n C1 n 3.020 8CP ₃ S-Vg n C1 n 3.021 OCP ₃ CH n C1 Vg 3.022 8CP ₃ CH n C1 Vg 3.023 8CP ₃ CH n Vg Me

Compounds of the general formula Ce) which are of particular interest:

No. [2- (6-chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxy- 80 016912 benzamide (compound No. 3.001 );

No. [2- (6-chloro-3-methoxy-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 3.002);

No. [2- (6-bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide ( compound No. 3.003);

No. [2- (6-bromo-7-methyl-2H- [1,2,3] triazolo [4,5-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide ( compound No. 3.004);

No. [2- (6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.005);

No. [2- (6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 3.006);

No. [2- (6-bromo-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.007 );

No. [2- (6-chloro-3-methoxy-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.008 );

No. [2- (6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.009);

No. [2- (6-chloro-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.010);

No. [2- (6-bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.011);

No. [2- (6-bromo-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 3.012);

No. [2- (6-bromo-7-methyl-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethylthiobenzamide (compound No. 3.023);

Ν- [1-cyano-2- (3,6-dichloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.017);

No. [2- (3-bromo-6-chloro-2H-pyrazolo [4,3-b] pyridin-2-yl) -1-cyano-1-methylethyl] -4-trifluoromethoxybenzamide (compound No. 3.019).

Numbers 3.001-3.012, 3.017, 3019 and 3.023 refer to the above compounds for identification and reference.

Method of application of examples

Method A. A screening method for testing the activity of compounds against soybean netisbik! Og1I8.

Twenty L1 larvae Nanoisybotic soybean are placed in the wells of a microtiter plate containing nutrient medium and test compound in DMSO. Then, the microtiter plate is maintained at 27 ° C, where L1 larvae are allowed to develop. The analysis is carried out on day 4 to determine successful development to stage b3. As a control, larvae are used; they are exposed to DMSO in the absence of the test compound. Connections numbered 1.002, 1.005, 1.006, 1.008, 1.009, 1.010, 1.011, 1.014, 1.017, 1.018, 1.025, 1.031, 1.045, 1.054, 1.055, 1.061, 1.076, 1.079, 1.081, 1.084, 2.004, 2.010, 2.020, 2.033 , 3.003 and 3.004 give at least 90% inhibition of motility at a test concentration of 0.15 ppm. on day 4 of the examination. Connections numbered 1.003, 1.007, 1.011, 1.015, 1.032, 1.038, 1.042, 1.043, 1.047, 1.048, 1.056, 1.057, 1.060, 1.066, 1.067, 1.070, 1.071, 1.075, 1.078, 2.001, 2.002, 2.003, 2.005, 2.006 , 2.007, 2.013, 2.015, 2.016, 2.021, 3.010 and 3.019 give at least 90% inhibition of motility at a test concentration of 0.04 ppm. on day 4 of the examination. Connections numbered 1.001, 1.012, 1.020, 1.021, 1.033, 1.034, 1.037, 1.039, 1.044, 1.085, 1.089, 1.091, 1.092, 1.093, 2.012, 2.014, 2.027, 2.028, 2.039, 3.005, 3.007, 3.008 and 3.017 give at least 90% inhibition of motility at a test concentration of 0.01 ppm on day 4 of the examination. Connections numbered 1.064, 1.065, 1.069, 1.083, 1.086, 1.087, 1.088, 1.090, 1.094, 1.095, 2.008, 2.009, 2.023, 2.024, 2.025, 2.026, 2.037, 2.038, 2.040, 2.041, 2.042, 2.043, 2.044, 2.045 , 2.046, 2.047, 2.048, 2.049, 2.050, 3.001, 3.002, 3.006, 3.009, 3.011, 3.012 and 3.023 give at least 90% inhibition of motility at a test concentration of 0.0025 ppm. on day 4 of the examination.

Method B. A screening method for testing the activity of compounds against Natoisbik soybean! Og! Ik 1 and y | yo in the Mongolian gerbil (Mepoyek iidschsi1a1ik).

Mongolian gerbils of at least five weeks of age are immunosuppressed and artificially infected with approximately 1000 third-stage encapsulated larvae of Naytoisbik soibobik. Six days after infection, Mongolian gerbils undergo oral administration of the test compounds dissolved in a mixture of 2 parts DMSO and 1 part polyethylene glycol (PEG 400) at doses of 10 and 1 mg / kg. As a control, gerbils treated only with placebo (2 parts DMSO and 1 part PEG 400 or pure PEG 400) in the absence of the test compound are used. On day 9 (3 days after treatment), gerbils are killed and opened to extract parasites from the stomach. Efficiency is calculated as the average percentage reduction in the number

- 81 016912 larvae in each test group in comparison with the average number of larvae from the control group. In each screening, a significant reduction in nematode infection was achieved in the presence of compounds of formula (I), especially from Table 1. 1-3. Compounds numbered 1.001, 1.008, 1.012, 1.013, and 1.014 provide at least a 95% reduction in nematode contamination in Mongolian gerbils subjected to oral forced administration of test compounds at a dose of 100 mg / kg. Compounds numbered 1.012, 1.033, 1.064, 2.008, 2.037, 2.038, 2.040, 2.041, 3.001 provide at least a 95% reduction in nematode infection at a dose of 10 mg / kg. Compounds numbered 1.094, 2.048, 3.001, 3.007 and 3.009 provide at least a 95% reduction in nematode infection at a dose of 1 mg / kg. Compounds numbered 3.005, 3.006, 3.011, 3.012, 3.017 and 3.019 provide at least a 95% reduction in nematode infection at a dose of 0.5 mg / kg.

Method C. Screening Method for Testing the Activity of Compounds Against Chrénocepyla1 ^ Chr5 Ge115.

Adults OeposeryShek Ge115 aged from three to five days (50) are aspirated into the test chamber. A separate glass cylinder, closed at one end with a self-tightening flexible film, is placed at the top of the test chamber in such a position that fleas can penetrate the film and feed on the contents of the glass cylinder. The test compound is dissolved in DMSO and added to bovine blood, which is then placed in a glass cylinder. DMSO treated blood serves as a control. Fleas are kept at 20-22 ° C, 40-60% relative humidity, while treated blood is at 37 ° C and 40-60% relative humidity. Treated blood is changed daily for six days, during which eggs and fecal matter are collected in a flea chamber. On day 6, the contents of each chamber are carefully inspected and placed in a saucer containing larval food, consisting of sand, mashed food for cats and dry cow blood. Saucers are kept at 28 ° C and 82% relative humidity for 11 days. Then the pupae are weeded out, weighed and returned to controlled conditions for an additional 5 days, after which the flight of adults is determined. The masses of pupae and the flight of adults are then compared with controls. Compounds numbered 1.012, 1.013, 1.020, 1.034, 1.064, and 3.005 give at least 80% reduction in the mass of pupae at a test concentration of 100 ppm. Connection number 2.048 gives at least 80% reduction in the mass of pupae at a test concentration of 25 ppm.

Method Ό. A screening method for testing the activity of compounds against Tps1, 511, 5, 5, 5, and 6.

Twenty larvae of L1 Tps1, 51Gotu1, and 5 s1bnGogt15 are placed in the wells of a microtiter plate containing nutrient medium and test compound in DMSO. Then, the microtiter plate is maintained at 27 ° C, where L1 larvae are allowed to develop. The analysis is carried out on day 4 to determine successful development to stage b3. The larvae are exposed to DMSO and do not use the test compound as a control. Compounds numbered 1.008, 1.014, 1.042, 1.047, 1.048, 1.073, 2.001, 2.003 and 2.020 give at least 90% inhibition of motility at a test concentration of 0.15 ppm. on day 4 of the examination. Connections numbered 1.001, 1.003, 1.007, 1.011,

I. 037, 1.038, 1.043, 1.056, 1.066, 1.070, 1.071, 2.012 and 2.016 give at least 90% inhibition of motility at a test concentration of 0.04 ppm. on day 4 of the examination. Compounds numbered 1.012, 1.020, 1.021, 1.033, 1.034, 1.039, 1.064, 1.065, 2.008, 2.009 and 3.005 give at least 90% inhibition of motility at a test concentration of 0.01 ppm. on day 4 of the examination. Compounds numbered 1.094, 2.040, 2.048, 2.049, 3.006, 3.009, 3.011 and 3.012 give at least 90% inhibition of motility at a test concentration of 0.0025 ppm. on day 4 of the examination.

Method E. Screening Method for Testing the Activity of Compounds Against Nanopotoxylate

II. 15, O51eg1ad1a ssitsts1a, Tps1u51gopdu1u5 akhe1, Tps1u51gopdu1u5 siubnGogt15, Soorepa sigNce1 and Nota1o61gn5 нin5 ίη u1uo in sheep.

Sheep was infected by the oral administration of infected at 3 stages with larvae (L3) O51g1ad1a sspitsts1a (~ 3,000 infected L3 per animal) per day -28, Nayot1c1sh5 ssUgC.15 (~ 2,000 infected L3 per animal) per day -25, Netaο ^^^ and 5 bp5 ~ 3,000 infected L3 per animal), T ^^ cL051 ^ οηdu1u5 akh1 (~ 3,000 infected L3 per animal) per day -23, Soorepa sig11ce1 (~ 3,000 infected L3 per animal) and T ^^ sb051 ^ οηdu1u5 co1uLnGogt15 (~ 3,000 B3 per animal) on day -21. A vaccination schedule has been developed so that the nematodes are matured on day 0. Test compounds are dissolved in DMSO / corn oil (1: 1) at a concentration of 100 mg / ml. The entire course of treatment is carried out by oral administration immediately on day 0. When the experimental animal is killed on day 15, the abomasum, small intestine and large intestine (including the cecum) are removed. Nematode counts are carried out in aliquots corresponding to 10% (abomasum and small intestine contents, abomasum absorption) or 20% (colon contents). All nematodes were subdivided into species or assigned to species based on the localization of regeneration (adult females, fourth stage larvae) for a total calculation per species. Efficiency is calculated as the percentage reduction in the average number of larvae in each test group compared to the decrease in the average number of larvae in the control group. In this screening, a significant reduction in nematode infection was achieved in the presence of compounds of formula (I), especially those presented in Table 1. 1-3. Compounds numbered 1.012 and 1.013 provide at least a 90% reduction in nematode infection at a dose of 30 mg / kg.

- 82 016912

In addition, compounds numbered 1.064, 1.094, 2.048, 3.005, 3.009 and 3.011 provide> 90% efficacy against one or more nematode species tested at such low doses as 1 or 3 mg / kg. For example, compound 3.009 provides> 95% efficacy against Tps1y51gopgu1u8 at a dose of 3 mg / kg, and compounds numbered 1.064, 1.094 and 2.048 provide> 95% efficacy against Naetopskik, O81g1ad1a, and Tps1y51gopdu1u5 at a dose of 3 mg / kg kg, and the compounds under the numbers 3.005 and 3.011 are more than 95% more effective against these parasites in such low doses as 1 mg / kg.

Method R. Screening method for testing the activity of compounds against microfilaria ΌηόГПапа ίιηιηίΐίδ.

From four hundred to six hundred microfilariae PnogPapa ίιηιηίΐίδ are placed in the wells of a microtiter plate containing a buffer and test compound in DMSO. Then, the microtiter plate is maintained at 37 ° C in an atmosphere containing 5% CO ₂ . Assessment is carried out after 24 hours to determine the survival of microfilariae. As a control, microfilariae exposed to DMSO are used without the participation of the test compound. Compounds numbered 1.003, 1.012, 1.013, 1.064, 1.086, 1.087, 1.090, 1.094, 2.043, 2.046, 2.047, 2.048, 2.049, 3.005, 3.006, 3.009, 3.011, 3.012, 3.017, 3.019, and 3.023 give at least 90% Inhibition of motility at a test concentration of 50 ppm

Thus, after various embodiments of the present invention have been described in detail, it becomes clear that the invention defined by the above paragraphs is not limited to the specific details set forth in the above description, since many obvious description options are possible without departing from the scope and essence of the present invention. .

Claims (28)

CLAIM 1. Aryloazol-2-ylcyanoethylamine of formula (I) where P is Ν; O is C-B ₂ or Ν; V represents С-В ₈ or Ν; W is C-B ₉ ; X is CB ₁₀ or Ν; Υ represents С-В _п or Ν; B ₂ B _8, B _{9 0} B1 and Bn are each independently of one another represent hydrogen, amino, amido, cyano, nitro, halogen, C1-C ₆ alkyl, C ₂ -C ₆ -alkenyl, C ₂ - C ₆ -alkynyl, C ₃ -C ₇ -cycloalkyl, hydroxy-C 1 -C ₆ -alkyl, halogen-C 1 -C ₆ -alkyl, C 1 -C ₆ -alkylthio, halogen-C 1 -C ₆ -alkylthio, arylthio, C 1 -C ₆ -alkoxy, phenoxy, C ₁ -C ₆ alkoxy-C ₁ -C ₆ alkoxy, C ₃ -C ₇ cycloalkyloxy, halogen-C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkylcarbonyl, halogen-C ₁ C ₆ alkylcarbonyl, C 1 -C 6 -alkylsulfonyl, halo-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6 alkylamino, di (C1-C6-alkyl) amino, C1-C6-alkylcarboxylamino, C1-C6-alkylamino C1-C6-alkoxy, diC1-C6-alkylamino-C1-C6-alkoxy, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, amino-C1-C6- alkyl, formyl, HO2C-, C1-C6-alkyl-O2C-, unsubstituted or substituted phenyl, or unsubstituted or substituted phenoxy, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-S6alkiltio, halo-C1-S6alkiltio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-S6alkilkarbonila, halo-C1-S6alkilkarbonila, C1- C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsul Onila and halo C1-C6 alkylsulfonyl; B3, B4 and B5, each independently of one another, represent hydrogen, C1-C6-alkyl, hydroxy-C1-C6 alkyl, C1-C6-alkylthio-C1-C6-alkyl, halogen-C1-C6-alkyl, C1-C6 -alkoxy-C1-C6-alkyl, C1-C6 alkylsulfinyl-C1-C6-alkyl, C1-C6-alkylsulfonyl-C1-C6-alkyl, C1-C6-alkylsulfonyloxy-C1-C6 alkyl; B6 is hydrogen, C1-C6-alkyl; B7 is unsubstituted or substituted phenyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C1-C6-alkyl, halogen-C1-C6-alkyl, phenyl, phenoxy, C1-C6-alkylthio, halogen -C1-C6-alkylthio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-S6alkilkarbonila, halo-C1-S6alkilkarbonila, C1-S6alkilsulfinila, halo-C1-S6alkilsulfinila, C1-C6 -alkylsulfonyl, halo-C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino and di (C 6 C 6 -alkyl) amino; unsubstituted or substituted hetaryl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 -alkyl, C 1 -C 6 alkylthio, halogen-C 1 -C 6-alkylthio, arylthio C 1 -C 6 alkoxy, halogen C 1 -C 6 alkoxy, C 1 -C 6 alkylcarbonyl, halogen-C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, halogen-C 1 -C 6- 83 016912 alkylsulfinyl, C 1 -CI-alkyl, alkyl, sulfonic, C 1 -C 6 alkyl-sulfonyl, C 1 -C 6 alkyl, sulfonic, haloalkyl -C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; or unsubstituted or substituted naphthyl or quinolyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 alkyl, C 1 -C 6 -alkylthio, halogen-C 1 -C 6- alkylthio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6 alkylcarbonyl, halo-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6 alkylsulfinyl, C1-C6-C6-C6-66 alkylsulfinyl, halogen-C1-alkyl, sulfonyl, halo-C1-6 alkylcarbonyl, C1-6alkylcarbonyl C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; where aryl represents a 6-10 membered aromatic ring and hetaryl represents a 4-7 membered monocyclic, 7-11 membered bicyclic or 10-15 membered tricyclic aromatic heterocycle containing 1, 2, 3 or 4 heteroatoms selected from, Oh, and 8; ζ is C (O), C (8) or 8 (Ο) ^ a is 1, 2 or 3; p is 0, 1 or 2; and its salts. 2. Aryloazol-2-ylcyanoethylamine according to claim 1, where O represents Ν; V is C ₈ ; X is C-K ₁₀ ; Υ represents CK ₁₁ ; Κ ₈ , Κ ₁₀ and K ₁₁ , each independently of one another, represent hydrogen, amino, amido, cyano, nitro, halogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ - alkynyl, C ₃ -C ₇ -cycloalkyl, hydroxy-C ₁ -C ₆ -alkyl, halo C1-C6 alkyl, C1-C6 alkylthio, halo C1-C6 alkylthio, arylthio, C1-C6 alkoxy, phenoxy, C1 -C6 alkoksiS1-C6-alkoxy, C3-C7-cycloalkyloxy, halo-C1-C6-alkoxy, C1-S6alkilkarbonil, halo-C1-S6alkilkarbonil, C1-C6-alkylsulfinyl, halo-C1-C6-alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino, di (C 1 -C 6 -alkyl) amino, C 1 -C 6 -alkylcarboxylamino, C 1 -C 6 alkylamino-C 1 -C 6 alcoh and diS1 -C6 alkylamino-C1 -C6 alkoxy, C1 -C6 alkylamino-C1 -C6 alkyl, diS1 -C6 alkylamino-C1 -C6 alkyl, amino-C ₁ -C ₆ alkyl, formyl, HO ₂ C-, C ₁ -C ₆ -alkyl-O ₂ C-, unsubstituted or substituted phenyl or unsubstituted or substituted phenoxy, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C1- C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkylthio, halo-C1-C6 alkylthio, arylthio, C1-C6-alkoxy, halogen-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halogen-C1- C6 alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl la and halogen-C1-C6-alkylsulfonyl; Κ ₃ , Β _4, and Κ ₆ represent hydrogen atoms; K ₅ is methyl; Κ-represents unsubstituted or substituted phenyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ -alkyl, phenyl, phenoxy, C ₁ -C ₆ -alkylthio, halo-C ₁ -C ₆ -alkylthio, arylthio, C ₁ -C ₆ -alkoxy, halogen-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ alkylcarbonyl, halogen-C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkylsulfinyl, halo-C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ alkylsulfonyl, C ₁ -C ₆ alkylamino and di (C ₁ -C ₆ -alkyl) amino; unsubstituted or substituted hetaryl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 -alkyl, halogen-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio, halogen-C 1 -C 6 -alkylthio , arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halo-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halo-C1-C6-alkylsulfinyl, C1 -C6 alkylsulfonyl , C1-C6-alkylamino and di (C1-C6-alkyl) amino; ζ is C (O) and a is 1; and its salts. 3. Aryloazol-2-ylcyanoethylamine according to claim 1, where O represents Ν; V is C ₈ ; X is C-K ₁₀ ; Υ represents CK ₁₁ ; Κ ₃ , Β _4, and Κ ₆ represent hydrogen atoms; K ₅ is hydrogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ -alkyl, hydroxy-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthioC ₁ -C ₆ -alkyl, C ₁ - C ₆ -alkyloxy-C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkylsulfonyloxy-C ₁ -C ₆ -alkyl; Κ-is unsubstituted phenyl or phenyl substituted by one or more substituents selected from the group consisting of C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ alkyl, phenyl, phenoxy, C ₁ -C ₆ alkoxy, halogen-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkylsulfinyl and halogen-C ₁ -C ₆ -alkylsulfonyl; Κ ₈ , ₁₀ and K ₁₁ , each independently of one another, represent hydrogen, halogen, C ₁ -C ₆ -alkyl, halogen-C ₁ -C ₆ -alkyl, cyano, C ₁ -C ₆ -alkoxy, halogen- C ₁ -C ₆ -alkoxy, C ₂ -C ₆ -alkenyl, C ₁ -C ₆ -alkylamino, hydroxy-C ₁ -C ₆ -alkyl, formyl, C ₁ -C ₆ -alkylamino-C ₁ -C ₆ - alkyl, BUT ₂ C-, C ₁ -C ₆ -alkyl-O ₂ C- or unsubstituted - 84 016912 or substituted phenyl, in which the substituents are C 1 -C 6 alkyl or halogen-C 1 -C 6 alkyl; ζ is C (O) and a is 1; and its salts. 4. Aryloazol-2-ylcyanoethylamine according to claim 1, where O represents Ν; V is C ₈ ; X represents C-KF; Υ represents CK ₁₁ ; K ₃ , K ₄ and K ₆ are hydrogen atoms; K ₅ is methyl, ethyl, butyl, CH ₂ OH, CH ₂ OCH ₃ , CH ₂ CCH ₃ or CH ₂ OO ₂ CH ₃ ; K ₇ is phenyl substituted with butyl, CP ₃ , phenyl, phenoxy, OCP ₃ , ZSR ₃ , OEDR ₃ or 8O ₂ CP ₃ ; K ₈ , K ₁₀ and K, each independently of one another, represent hydrogen, methyl, CH ₂ MH ₂ , CH ^ (CH ₃ ) ₂ , vinyl, CH ₂ OH, CH (OH) CH ₂ OH, CO ₂ H, CO ₂ CH ₃ , PP-CP ₃ , P, C1, Br, CP ₃ , OCP ₃ or; ζ is C (O) and a is 1; and its salts. 5. Aryloazol-2-ylcyanoethylamine according to claim 1, where O is CK ₂ ; V is C ₈ ; X represents C-KF; Υ represents C-Cc; K2 is hydrogen, C1, methyl, methoxy, ethoxy, propoxy, butoxy, O (CH2) 2OCH3 or O (CH2HCN ₃ b; K ₃ , K ₄ and K ₆ are hydrogen atoms; K ₅ is methyl; K ₇ is phenyl, substituted OCP ₃ , phenoxy or CSR ₃ ; K _8, K ₁₀ and itz, each independently, represent hydrogen, C1, Br, _C1-C6 alkyl, SR _3, nitro, amino, amido, CO ₂ CH ₃ or MNSOSN _3; ζ is C (O) and a is 1; and its salts. 6. Aryloazol-2-ylcyanoethylamine according to claim 1, where O is CK ₂ or Ν; V represents Ν; X is C-K ₁₀ ; Υ represents C- _n ; K ₂ is hydrogen, C1, Br or methoxy; K3, K4 and K6 are hydrogen atoms; K5 is methyl; K ₇ is phenyl substituted with OCP ₃ or CSR ₃ ; K ₁₀ and Itz, each independently of one another, are hydrogen, C1, Br or methyl; ζ is C (O) and a is 1; and its salts. 7. A pesticidal composition having activity against endo- and ectoparasites, containing from 0.05 to 10% (w / v) of a compound according to claim 1 and a pesticidal or veterinary acceptable carrier. 8. The pesticide composition according to claim 7, which, in addition, contains an additional pesticidal compound. 9. The method of obtaining the compounds of formula (I) according to claim 1, which includes: (ί) production of a carbonyl compound of formula (IV) by reacting ΝΉ-arylazole of general formula (V) with a compound of general formula (VI) ΝΗ Lake is a base where P represents Ν; O is CK ₂ or Ν; - 85 016912 V is C ₈ or Ν; V is C ₉ ; X is C-K ₁₀ or Ν; Υ represents CK _p or Ν, K ₂ K _8, R _9, R ₁₀ and R, each independently, represent hydrogen, amino, amido, cyano, nitro, halogen, C1-C ₆ alkyl, C ₂ -C ₆ -alkenyl, C ₂ - C ₆ -alkynyl, C ₃ -C ₇ -cycloalkyl, hydroxy-C 1 -C ₆ -alkyl, halogen-C 1 -C ₆ -alkyl, C 1 -C ₆ -alkylthio, halogen-C 1 -C ₆ -alkylthio, arylthio, C 1 -C ₆ -alkoxy, phenoxy, C ₁ -C ₆ alkoxy-C ₁ -C ₆ alkoxy, C ₃ -C ₇ cycloalkyloxy, halogen-C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkylcarbonyl, halogen-C ₁ C ₆ -alkylcarbonyl, C 1- C ₆ -alkilsulfinil, _halo-C1-C6 -alkilsulfinil, _C1-C6 alkylsulfonyl, C ₁ -C ₆ alkylamino, di (C1-C ₆ alkyl) amino, _C1-C6 -alkilkarboksilamino, _C1-C6 -but kilamino _C1-C6 alkoxy, diS1 -C6 alkylamino-C1 -C6 alkoxy, C1 -C6 alkylamino-C1 -C6 alkyl, diS1 -C6 alkylamino-C1 -C6 alkyl, amino-C1 -C6-alkyl, formyl, HO2C-, C1-C6-alkyl-O2C-, unsubstituted or substituted phenyl or unsubstituted or substituted phenoxy, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C1-C6 -alkyl, halo-C1-C6-alkyl, C1-C6-alkylthio, halo-C1-C6 alkylthio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkylcarbonyl, halo-C1-C6 alkylcarbonyl , C1-C6-alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6 -alkylsulfonyl and halogen-C1-C6-alkylsulfonyl; K3, K4 and K5, each independently of one another, represent hydrogen, C1-C6-alkyl, hydroxy-C1-C6 alkyl, C1-C6-alkylthio-C1-C6-alkyl, halogen-C1-C6-alkyl, C1-C6 -alkoxy-C1-C6-alkyl, C1-C6 alkylsulfinyl-C1-C6-alkyl, C1-C6-alkylsulfonyl-C1-C6-alkyl or C1-C6-alkylsulfonyloxy-C1-C6 alkyl; a is 1, 2 or 3; T represents a leaving group; (ίί) obtaining a derivative of α-aminonitrile of formula (II) by reacting a carbonyl compound of general formula (IV) containing a source of cyanide with an amine of general formula K ₆ -IN ₂ in the presence of an ammonium salt I Ν - (C) a — n — K, ------ N Suuyez (IV) (II) Suashiev - Cyanides where K ₃ , Cd, K ₅ , P, O, V, V, X, Υ and a are defined above and K ₆ is hydrogen or C 1 -C ₆ alkyl; and (br) the interaction of the compounds of formula (II) with compound (III) in the presence of a base in a solvent where K ₃ , Cd, K ₅ , Kb, P, O, V, V, X, and a are defined above; K7 represents a substituted or unsubstituted phenyl wherein the substituents are independently selected from the group consisting of cyano, nitro, halogen, _C1-C6 alkyl, halo _C1-C6 alkyl, phenyl, phenoxy, C1-C ₆ - alkylthio, _halo-C1-C6 alkylthio, arylthio, _C1-C6 alkoxy, halo C1-C ₆ -alkoxy, C ₁ -C ₆ alkylcarbonyl, _halo-C1-C6 alkylcarbonyl, C1-C ₆ - alkylsulfinyl, _halo-C1-C6 alkylsulfinyl, S1S6-alkylsulfonyl, halo-S1S6-alkylsulfonyl, S1S6-alkylamino and di (S1S6-alkyl) amino; unsubstituted or substituted hetaryl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 -alkyl, C 1 -C 6 alkylthio, halogen-C 1 -C 6-alkylthio, arylthio C 1 -C 6 alkoxy, halogen-C 1 -C 6 alkoxy, C 1 -C 6 alkylcarbonyl, halogen-C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, halogen-C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, -halo-halogen-C6-C6 alkylsulfonyl, C 1 -C 6 -alkylsulfonyl, -halo-halogen-C6-alkylsulfonyl; -alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; or unsubstituted or substituted naphthyl or quinolyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 alkyl, C 1 -C 6 -alkylthio, halogen-C 1 -C 6- alkylthio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6 alkylcarbonyl, halo-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6 alkylsulfinyl, C1-C6-C6-C6-66 alkylsulfinyl, halogen-C1-alkyl, sulfonyl, halo-C1-6 alkylcarbonyl, C1-6alkylcarbonyl C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; ζ is C (O), C (8) or 8 (O) _p ; p is 0, 1 or 2; T represents a leaving group. 10. A method of treating endoparasitic infection in an animal, which comprises administering to the animal an effective amount of a compound according to claim 1. - 86 016912 11. A method of making a living in it. SgaGegokGotit, P1s (uosai1ik, P1re (a1opeta, P1ru11bsht, Pyoy1aya, Pgasipsi1ik, EsYposossik, EpGegoshk, Raksyu1a, R11ago1bek, Nagopeta, Naetopsyik, Megakom (gopdu1ik, Moη eζ ^ ^ a YesaGog, YetaGobpik, №rrokyopdu1ik, OekoryadokGitit, Opsyosegsa, OkGeyad1a , Ohuipk, Ragasapk, 8СЫкГокота, 8Гг Oppdukik, Taesha, Tokhosaga, 8Ggopdu1o1bek, Tokhaksapk, Tpsype11a, Tpsyipk, Tpsyokyopdu1ik, TpobopGoryogoik, Ipshapa, Huygegepa and their combinations. 12. The method of claim 11, wherein the worms are Naetopsyik sopGoyik, OkGeyad1a sysitsts (a, Tpsyok1gopduy1k ahe1, TpsyokGgopdu1ik so1ipGogsh1k, Soorepa sshPser YetaGob1gik ayik and combinations thereof. 13. The method according to claim 12, where the helminths are Naethoxy coxoic and the compound is a compound of formula (I), in which P represents Ν; O is CK ₂ or Ν; ν is C — K ₈ or Ν; V is C ₉ ; X represents CK. ₁₀ ; Υ represents CK ₁₁ ; K ₂ is hydrogen, C1, Br, methyl or methoxy; K3, K4 and K6 are H; K5 is methyl; K- is phenyl, substituted by OCP ₃ , 8CP ₃ or CHPCP ₃ ; K ₈ is H, C1, Br, P or ί.'Ν; K ₉ is H, C1 or Br; K ₁₀ is H, C1, Br or CP ₃ ; Bp is H, C1, Br or methyl; ζ is C (O) and a is 1. 14. The method according to claim 12, wherein the helminths are Naethopsyc conjugate and the compound is a compound of formula (I) in which ν is; X represents CK. ₁₀ ; Υ represents CK ₁₁ ; K ₂ is hydrogen, C1, Br, methyl or methoxy; K3, K4 and K6 are H; K ₅ is methyl; is phenyl, substituted by OCP ₃ or 8CP ₃ ; K ₉ represents H; K ₁₀ is C1 or Br; K11 is H; ζ is C (O) and a is 1. 15. A method of treating an ectoparasitic infection in an animal, which comprises administering to the animal an effective amount of a compound according to claim 1. 16. The method of claim 15, wherein the ectoparasitic infection is caused by an ectoparasite selected from the group consisting of fleas, ticks, mosquitoes, flies, lice, meat flies, and combinations thereof. 17. The method according to p. 16, in which the ectoparasitic infection are fleas. 18. The method of obtaining aryloazol-2-yl-cyanoethylamine according to claim 1, where O is CH, which includes: (a) the interaction of the compounds of formula (XIV) (XIV) with the compound of the formula (XV) Μ + γ '* ¹⁴ * 16 (XV) to form a compound of formula (XIII) - 87 016912 where V represents С-К ₈ or Ν; represents C ₉ ; X is C-K ₁₀ or Ν; Υ represents the CK. _n or Ν; By _8, R _9, R ₁₀ and R, each independently, represent hydrogen, amino, amido, cyano, nitro, halogen, C1-C ₆ alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₇ -cycloalkyl, hydroxy-C 1 -C ₆ -alkyl, halogen-C 1 -C ₆ -alkyl, C 1 -C ₆ -alkylthio, halogen-C 1 -C ₆ -alkylthio, arylthio, C 1 -C _6- alkoxy, phenoxy, C ₁ -C ₆ alkoxy-C ₁ -C ₆ alkoxy, C ₃ -C ₇ cycloalkyloxy, halogen-C ₁ -C ₆ alkoxy, C ₁ -C ₆ -alkylcarbonyl, halogen-C 1 C6-alkylcarbonyl, C ₁ -C ₆ -alkylsulfinyl , halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6 alkylamino, di (C1-C6-alkyl) amino, C1-C6-alkylcarboxylamino, C1-C6-alkylamino-C1- 6-alkoxy, diC1-C6-alkylamino-C1-C6-alkoxy, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, amino-C1-C6-alkyl, formyl, HO2C-, C1-C6-alkyl-O2C-, unsubstituted or substituted phenyl or unsubstituted or substituted phenoxy, where the substituents are independently from each other selected from the group consisting of cyano, nitro, halogen, C1-C6-alkyl, halogen C1-C6-alkyl, C1-S6alkiltio, halo-C1-S6alkiltio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-S6alkilkarbonila, halo-C1-S6alkilkarbonila, C1-C6 alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6 alkylsulfone sludge and halogen-C1-C6-alkylsulfonyl; K ₁₆ is halogen or trifluoromethanesulfonyl; ₄ K1 and K15 are independently _C1-C4 alkyl or _{C1-C4-alkylcarbonyl} and M is trialkyltin, boric acid or boric acid ester; the introduction of the compounds of formula (XIII) in the oxidative cleavage with the formation of the compounds of formula (X) the interaction of the compounds of formula (X) with the compound of the formula (XI) C 1 -C ₆ -alkylsulfonyl-C 1 -C ₆ alkyl, C1-S6v which K _3, K ₄ and K ₅ each independently represent hydrogen, halogen, C ₁ -C ₆ alkyl, _{hydroxy-C1-C6} alkyl, _C1-C6 alkylthio-C1-C _6- alkyl, halo-C 1 -C ₆ -alkyl, C 1 -C ₆ -alkoxy-C 1 -C ₆ alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, alkylsulfonyloxy-C 1 -C 6 -alkyl; and K1 ₂ is a hydroxy protecting group, with the formation of a compound of formula (IX), the introduction of a compound of formula (IX) into a heterocyclization stage to form a compound of formula (VIII); - 88 016912 O * ³ M- (C) and η-κ ₅ it CH (VII) where O is CH; and oxidizing a compound of formula (VII) to form a compound of formula (IV), where O represents (IV) (b) the reaction of a compound of formula (IV) with B ₆ -IN ₂ to form a compound of formula (II) (I) where B6 represents hydrogen or C1-C6 alkyl; and (c) the interaction of the compounds of formula (II) with Τ-Ζ-Κ ₇ , where T represents a leaving group; Ζ is C (O), C (8) or 8 (O) p; B ₇ represents unsubstituted or substituted phenyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C ₆ alkyl, halogen-C 1 -C ₆ alkyl, phenyl, phenoxy, C 1 -C ₆ alkylthio, _halo-C1-C6 alkylthio, arylthio, _C1-C6 alkoxy, halo C1-C ₆ -alkoxy, C ₁ -C ₆ alkylcarbonyl, _halo-C1-C6 alkylcarbonyl, _C1-C6 -alkilsulfinila, halo _C1-C6 alkylsulfinyl, S1S6-alkylsulfonyl, halo-S1S6-alkylsulfonyl, S1S6-alkylamino and di (S1S6-alkyl) amino; unsubstituted or substituted hetaryl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 -alkyl, C 1 -C 6 alkylthio, halogen-C 1 -C 6-alkylthio, arylthio C 1 -C 6 alkoxy, halogen-C 1 -C 6 alkoxy, C 1 -C 6 alkylcarbonyl, halogen-C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, halogen-C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, -halo-halogen-C6-C6 alkylsulfonyl, C 1 -C 6 -alkylsulfonyl, -halo-halogen-C6-alkylsulfonyl; -alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; or unsubstituted or substituted naphthyl or quinolyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 alkyl, C 1 -C 6 -alkylthio, halogen-C 1 -C 6- alkylthio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6 alkylcarbonyl, halo-C1-C6-alkylcarbonyl, C1-C6-alkylsulfinyl, halogen-C1-C6 alkylsulfinyl, C1-C6-C6-C6-66 alkylsulfinyl, halogen-C1-alkyl, sulfonyl, halo-C1-6 alkylcarbonyl, C1-6alkylcarbonyl C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; in the presence of a base to form a compound of formula (I) according to claim 1, wherein P is Ν; O is CH; V represents С-В ₈ or Ν; W is C-B ₉ ; X is CB ₁₀ or Ν; Υ represents C-Bc or Ν; B _8, B _{9 0} B1 and Bn are each independently of one another represent hydrogen, amino, amido, cyano, nitro, halogen, C1-C ₆ alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₇ -cycloalkyl, hydroxy-C 1 -C ₆ -alkyl, halogen-C 1 -C ₆ -alkyl, C 1 -C ₆ -alkylthio, halogen-C 1 -C ₆ -alkylthio, arylthio, C 1 -C ₆ -alkoxy, phenoxy, _C1-C6 alkoxy S1S6-alkoxy, C3-C7-cycloalkyloxy, halogen-S1S6 alkoxy S1S6-alkylcarbonyl, halo-S1S6 alkylcarbonyl, S1S6 alkylsulfinyl, halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6 alkylamino, di (C1-C6-alkyl) amino, C1-C6-alkylcarboxylamino, C1-C6-alkylamino-C1-C6 -alkoxy, diC1-C6-alkylamino-C1-C6-alkoxy, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, amino-C1-C6-alkyl, formyl , HO2C-, C1-C6-alkyl-O2C-, unsubstituted or substituted phenyl or unsubstituted or substituted phenoxy, where the substituents are independently from each other selected from the group consisting of cyano, nitro, halogen, C1-C6-alkyl, halogen-C1 -S6-alkyl, C1-S6alkiltio, halo-C1-S6alkiltio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-S6alkilkarbonila, halo-C1-S6alkilkarbonila, C1-C6 alkylsulfinyl , halogen-C1-C6-alkylsulfinyl, C1-C6-alkylsulfonium la and - 89 016912 halogen-C1-C ₆ -alkylsulfonyl; K3, K4 and K5 are each independently of one another represent hydrogen, C1-C6alkyl, hydroxy-C1-C6alkyl, _C1-C6 alkylthio _C1-C6 alkyl, halo _C1-C6 alkyl, C ₁ -C ₆ alkoxy-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylsulfinyl-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylsulfonyl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkyl sulfonyloxy-C ₁ -C ₆ alkyl; K6 is hydrogen, C1-C6-alkyl; K7 is unsubstituted or substituted phenyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C1-C6-alkyl, halogen-C1-C6-alkyl, phenyl, phenoxy, C1-C6-alkylthio, halogen -C1-C6-alkylthio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-S6alkilkarbonila, halo-C1-S6alkilkarbonila, C1-S6alkilsulfinila, halo-C1-S6alkilsulfinila, C1-C6 -alkylsulfonyl, halo-C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino and di (C 6 C 6 -alkyl) amino; unsubstituted or substituted hetaryl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 -alkyl, C 1 -C 6 alkylthio, halogen-C 1 -C 6-alkylthio, arylthio C 1 -C 6 alkoxy, halogen-C 1 -C 6 alkoxy, C 1 -C 6 alkylcarbonyl, halogen-C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, halogen-C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, -halo-halogen-C6-C6 alkylsulfonyl, C 1 -C 6 -alkylsulfonyl, -halo-halogen-C6-alkylsulfonyl; -alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; or unsubstituted or substituted naphthyl or quinolyl, where the substituents are independently selected from the group consisting of cyano, nitro, halogen, C 1 -C 6 alkyl, halogen-C 1 -C 6 alkyl, C 1 -C 6 -alkylthio, halogen-C 1 -C 6- alkylthio, arylthio, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-S6alkilkarbonila, halo-C1-S6alkilkarbonila, C1-S6alkilsulfinila, halo-C1-S6alkilsulfinila, C1-C6-alkylsulfonyl, halo- C1-C6-alkylsulfonyl, C1-C6-alkylamino, di (C1-C6 alkyl) amino; ζ is C (O), C (8) or 8 (O) _P ; a is 1, 2 or 3 and p is 0, 1 or 2. 19. The compound according to claim 1 of the formula Ce) where K = 8CP3 or OCP3; P = C-K2; K ₂ is hydrogen, Br, P, C1, methyl, methoxy, ethoxy or propoxy, and K ₉ , K ₁₀ and Kp each independently represent H, halogen or C 1 -C ₆ alkyl. 20. The compound according to claim 19, where K ₂ is H, Br or methoxy, and K ₉ , K ₁₀ and Kn, each independently, represent H, Br or C1. 21. The compound according to claim 19, where K2 represents H and K ₉ , K ₁₀ and K _p , each independently, represent H, Br or C1. 22. The compound according to claim 21, where K represents OCP3; K2 is H; K9 and K11 represent H; K ₁₀ represents Br. 23. The compound according to claim 1 of the formula CB) where K = 8CP ₃ or CP ₃ ; K ₂ is hydrogen, Br, P, C1, methyl, methoxy, ethoxy, propoxy, butoxy, O (CH ₂ ) ₂ OCH ₃ or O (CH 2 HS 3) 2 and K ₈ , K ₉ , K ₁₀ and Kp each independently represent H, halogen, nitro, amino, amido, alkylcarbonylamino, HO ₂ C-, alkyl-O ₂ C-, halogen-C 1 -C ₆ -alkyl or C 1- C ₆ -alkyl. 24. The compound according to claim 23, wherein K ₂ is hydrogen, Br, C1, methyl, methoxy or ethoxy and К ₈ , К ₉ , К ₁₀ and К „, each independently represent H, С1, Вг, methyl, СР ₃ or nitro. 25. The compound according to claim 23, wherein K2 is hydrogen or methoxy; and - 90 016912 K ₈ , K ₉ , K ₁₀ and Itz, each independently, represent H, C1 or Br. 26. The compound according to claim 1 of the formula (! C) where K = 8CP ₃ or OCP ₃ ; K ₅ is C 1 -C ₆ alkyl, hydroxyalkyl, alkylthioalkyl or alkylsulfonyloxyalkyl and K ₈ , K ₉ , K ₁₀ and IC, each independently represent H, halogen, cyano, amino, aminoalkyl, alkylaminoalkyl, formyl, HO ₂ C-, alkyl-O ₂ C-, halogen-C1-C ₆ -alkyl, _C1-C6 alkyl, _C1-C6 alkenyl, _C1-C6 alkoxy or halo _C1-C6 alkoxy. 27. The compound according to claim 26, wherein To ₅ represents _C1-C6 alkyl or hydroxyalkyl, and K ₈ , K ₉ , Kyu and Itz each independently represent H, halogen, HO ₂ C-, alkyl-O ₂ C-, halogen-C 1 -C ₆ alkyl, C 1 -C ₆ -alkyl, C 1 -C ₆ - alkoxy or _halo-C1-C6 alkoxy. 28. The compound according to claim 27, wherein K ₅ is methyl or hydroxyalkyl and K ₈ , K ₉ , K ₁₀ and K _p each independently represent H, methyl, CP ₃ , C1, Br, P, methoxy or trifluoromethoxy.